A PHASE 2B PLACEBO-CONTROLLED, RANDOMIZED STUDY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE IN PREGNANT WOMEN

Respiratory Tract Infection Clinical Trial

Official title:

A PHASE 2B, RANDOMIZED, PLACEBO-CONTROLLED, OBSERVER-BLINDED TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINE IN PREGNANT WOMEN 18 THROUGH 49 YEARS OF AGE AND THEIR INFANTS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04032093
• Other study ID #: C3671003
• Status: Completed
• Phase: Phase 2
• Start date: August 7, 2019
• Est. completion date: September 30, 2021

Study information

• Verified date: September 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 2b study will evaluate the safety, tolerability, and immunogenicity of an RSV vaccine in pregnant participants who receive either one of 2 dose levels of the vaccine, formulated with or without aluminum hydroxide, or placebo, and investigate safety and characteristics of antibodies in their infants.

Description:

This Phase 2b, multicenter, randomized, placebo-controlled study will evaluate the safety, tolerability, and immunogenicity of a respiratory syncytial virus stabilized prefusion F subunit vaccine (RSV vaccine) in pregnant participants who receive either one of 2 dose levels of the vaccine, formulated with or without aluminum hydroxide, or placebo, as well as assess safety and characteristics of transplacentally transferred antibodies in their infants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1153
• Est. completion date: September 30, 2021
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria - Maternal participants:

• Healthy women 18 to 49 years of age between 24 and 36 weeks of gestation on the day of planned vaccination, with an uncomplicated pregnancy, who are at no known increased risk for complications, and whose fetus has no significant abnormalities observed on ultrasound.

• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

• Receiving prenatal standard of care.

• Had an ultrasound performed at >=18 weeks of pregnancy.

• Had a negative urinalysis for protein and glucose at the screening visit. Trace protein in the urine is acceptable if the blood pressure is also normal.

• Determined by medical history, physical examination, screening laboratory assessment, and clinical judgment to be appropriate for inclusion in the study.

• Documented negative human immunodeficiency virus antibody, hepatitis B virus surface antigen, hepatitis C virus antibody, and syphilis tests at the screening visit.

• Body mass index of </=40 kg/m2 at the time of the screening visit.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document and in this protocol.

• Expected to be available for the duration of the study and willing to give informed consent for her infant to participate in the study.

Inclusion Criteria - Infant Participants:

• Evidence of a signed and dated ICD signed by the parent(s).

• Parent(s) willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria - Maternal Participants:

• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the investigational product or any related vaccine.

• History of latex allergy.

• History of any severe allergic reaction.

• Participants with known or suspected immunodeficiency.

• Current pregnancy resulting from in vitro fertilization or other assisted reproductive technology.

• A prior history of or known current pregnancy complications or abnormalities that will increase the risk associated with the participant's participation in and completion of the study.

• Major illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in, and completion of, the study or could preclude the evaluation of the participant's response.

• Participant with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not limited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and insulin-dependent diabetes mellitus (type 1).

• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

• Participation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study participation.

• Participants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (such as for cancer or an autoimmune disease), or planned receipt of such treatment or agents during study participation. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

• Current alcohol abuse or illicit drug use.

• Receipt of blood or plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt through delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.

• Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.

• Laboratory test results at the screening visit outside the normal reference value for pregnant women according to their trimester in pregnancy.

• Participants who are breastfeeding at the time of the screening visit.

Exclusion Criteria - Infant Participants:

• Infant who is a direct descendant (eg, child or grandchild) of the study personnel.

Related Conditions & MeSH terms

• Respiratory Tract Infection
• Respiratory Tract Infections

Intervention

Biological:
• RSV vaccine
RSV vaccine
• Placebo
Normal saline solution for injection (0.9% sodium chloride injection)

Locations

Country	Name	City	State
Argentina	Clinica Mayo De U.M.C.B. S.R.L.	San Miguel de Tucuman	Tucuman
Argentina	Instituto de Maternidad y Ginecologia, Nuestra Senora de Las Mercedes	San Miguel de Tucuman	Tucuman
Chile	Hospital Base San Jose de Osorno	Osorno	Región DE LOS Lagos
Chile	Centro Internacional de Estudios Clinicos - CIEC	Santiago	Región Metropolitana
Chile	Clinica Universidad de los Andes	Santiago	Región Metropolitana
Chile	Grupo Estudios Clinicos Infectologia Respiratoria, Facultad de Medicina Universidad de Chile	Santiago	Región Metropolitana
Chile	Hospital Clinico Universidad de Chile	Santiago	Region Metropolitana
Chile	Hospital Padre Hurtado	Santiago	Region Metropolitana
Chile	Hospital San Borja Arriaran	Santiago	RM
Chile	Hospital San Jose	Santiago	Región Metropolitana
Chile	Instituto de Investigaciones Materno Infantil (IDIMI)	Santiago	Región Metropolitana
New Zealand	Christchurch Clinical Studies Trust Ltd	Christchurch
New Zealand	Christchurch Hospital (Canterbury District Health Board)	Christchurch
South Africa	Respiratory and Meningeal Pathogens Research Unit (RMPRU)	Soweto	Gauteng
United States	MedPharmics	Albuquerque	New Mexico
United States	Cambridge Medical Trials	Alexandria	Louisiana
United States	The Iowa Clinic	Ankeny	Iowa
United States	Emory Children's Center	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Colorado Anschutz Inpatient Pavilion 2	Aurora	Colorado
United States	University of Colorado AO1	Aurora	Colorado
United States	University of Colorado Hospital Inpatient Pavilion	Aurora	Colorado
United States	University of Colorado Hospital Outpatient Pavilion	Aurora	Colorado
United States	University of Colorado Leprino Building	Aurora	Colorado
United States	University of Colorado Research II Building	Aurora	Colorado
United States	Oshsner Medical Center - Hancock	Bay Saint Louis	Mississippi
United States	Center for Women''s Health and Birthcare	Beaumont	Texas
United States	CHRISTUS St. Elizabeth Hospital	Beaumont	Texas
United States	Gadolin Research, LLC	Beaumont	Texas
United States	Pediatric Clinic of Dr. Alvin H. Prause	Beaumont	Texas
United States	Texas Health Harris Methodist Hurst-Euless-Bedford Hospital	Bedford	Texas
United States	Join Clinical Trials	Bellflower	California
United States	Merit Health Biloxi	Biloxi	Mississippi
United States	Children's of Alabama	Birmingham	Alabama
United States	UAB Women & Infants Center - UAB Medicine	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Bingham Memorial Hospital	Blackfoot	Idaho
United States	Elite Clinical Trials LLLP	Blackfoot	Idaho
United States	Grove Creek Medical Center	Blackfoot	Idaho
United States	Allina Health Blaine Clinic	Blaine	Minnesota
United States	Texas Health Huguley Hospital South	Burleson	Texas
United States	St Lukes Hospital	Chesterfield	Missouri
United States	Chowchilla Hospital Clinic	Chowchilla	California
United States	Allina Health Coon Rapids Clinic	Coon Rapids	Minnesota
United States	Allina Health Mercy Women's Clinic	Coon Rapids	Minnesota
United States	Mercy Hospital (Allina Health)	Coon Rapids	Minnesota
United States	The Mother Baby Center at Mercy with Children's (Allina Health)	Coon Rapids	Minnesota
United States	Cullman Clinical Research, Inc	Cullman	Alabama
United States	Cullman Primary Care, PC	Cullman	Alabama
United States	Cullman Regional	Cullman	Alabama
United States	Kettering Medical Center	Dayton	Ohio
United States	Needmore Medical Center	Dayton	Ohio
United States	Sugarcamp Family Practice	Dayton	Ohio
United States	Duke Children's Primary Care - Roxboro Street	Durham	North Carolina
United States	Duke Regional Hospital	Durham	North Carolina
United States	Duke University Hospital	Durham	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Alliance for Multispecialty Research, LLC	El Dorado	Kansas
United States	HWC Women's Center Research	Englewood	Ohio
United States	8th Avenue Obstetrics and Gynecology	Fort Worth	Texas
United States	Baylor Scott & White of Fort Worth	Fort Worth	Texas
United States	Texas Health Harris Methodist Hospital FTW	Fort Worth	Texas
United States	Texas Health Harris Methodist Hospital Southwest	Fort Worth	Texas
United States	Ventavia Research Group, LLC	Fort Worth	Texas
United States	Allina Health Fridley Clinic	Fridley	Minnesota
United States	University of Texas Medical Branch	Galveston	Texas
United States	Chisholm Trail Pediatrics	Georgetown	Texas
United States	FMC Science, LLC	Georgetown	Texas
United States	Georgetown OBGYN	Georgetown	Texas
United States	St. David's Georgetown Hospital	Georgetown	Texas
United States	Arrowhead Hospital	Glendale	Arizona
United States	Abrazo West Campus Hospital	Goodyear	Arizona
United States	Baylor Scott & White of Grapevine (Hospital)	Grapevine	Texas
United States	Boeson Research	Great Falls	Montana
United States	Gulfport Memorial Hospital	Gulfport	Mississippi
United States	Gulfport OB-GYN	Gulfport	Mississippi
United States	MedPharmics, LLC	Gulfport	Mississippi
United States	Singing River Health System	Gulfport	Mississippi
United States	Winthrop Women's Wellness	Hempstead	New York
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Dr Van Tran Family Practice	Houston	Texas
United States	HG Pediatrics	Houston	Texas
United States	Memorial Herman Greater Heights Hospital	Houston	Texas
United States	Texas Center for Drug Development, Inc.	Houston	Texas
United States	Ventavia Research Group, LLC	Houston	Texas
United States	Cabell Huntington Hospital	Huntington	West Virginia
United States	Marshall Health dba University Pediatrics	Huntington	West Virginia
United States	Marshall Health Department of Obstetrics and Gynecology	Huntington	West Virginia
United States	Translational Genomic Research Institute	Huntington	West Virginia
United States	Join Clinical Trials	Huntington Park	California
United States	Matrix Clinical Research	Huntington Park	California
United States	Hutchinson Clinic, P.A.	Hutchinson	Kansas
United States	Hutchinson Regional Medical Center	Hutchinson	Kansas
United States	Clinical Research Prime	Idaho Falls	Idaho
United States	Eastern Idaho Regional Medical Center	Idaho Falls	Idaho
United States	Family First Medical Center	Idaho Falls	Idaho
United States	Mountain View Hospital	Idaho Falls	Idaho
United States	Snake River Research, PLLC	Idaho Falls	Idaho
United States	The Pediatric Center	Idaho Falls	Idaho
United States	Sante Comprehensive Women's Healthcare	Johnson City	New York
United States	AdventHealth Family Medicine Rural Health Clinic, Inc.	Lampasas	Texas
United States	FMC Science	Lampasas	Texas
United States	Bryan Health	Lincoln	Nebraska
United States	Bryan Women's Care Physicians	Lincoln	Nebraska
United States	Midwest Childrens Health Research Institute	Lincoln	Nebraska
United States	DCOL Center For Clinical Research	Longview	Texas
United States	Diagnostic Clinic of Longview	Longview	Texas
United States	Longview Regional Medical Center	Longview	Texas
United States	East Los Angeles Doctors Hospital	Los Angeles	California
United States	Join Clinical Trials	Los Angeles	California
United States	Join Clinical Trials	Los Angeles	California
United States	Matrix Clinical Research	Los Angeles	California
United States	White Memorial Medical Center	Los Angeles	California
United States	Affiliated Physician Practice	Madera	California
United States	Charles E. Ugwu-Oju, MD, FACOG	Madera	California
United States	Madera Community Hospital	Madera	California
United States	Madera Family Medical Group	Madera	California
United States	Dr. Ruben Aleman and Associates	McAllen	Texas
United States	MedPharmics, LLC	Metairie	Louisiana
United States	NYU Winthrop Hospital	Mineola	New York
United States	NYU Winthrop Hospital, Research Pharmacy	Mineola	New York
United States	NYU Winthrop Pediatric Infectious Diseases	Mineola	New York
United States	Women's Contemporary Care Associates	Mineola	New York
United States	Abbott Northwestern Hospital (Allina Health)	Minneapolis	Minnesota
United States	Infectious Disease Research	Minneapolis	Minnesota
United States	Boeson Research	Missoula	Montana
United States	Monterey Park Hospital	Monterey Park	California
United States	Intermountain Medical Center	Murray	Utah
United States	ASR, LLC	Nampa	Idaho
United States	Saltzer Medical Group	Nampa	Idaho
United States	Saltzer Medical Group	Nampa	Idaho
United States	Meridian Clinical Research, LLC	Norfolk	Nebraska
United States	Exygon Clinical Research	Pharr	Texas
United States	MedPharmics, LLC	Phoenix	Arizona
United States	St. Joseph Hospital	Phoenix	Arizona
United States	Texas Health Presbyterian Hospital	Plano	Texas
United States	Ventavia Research Group LLC	Plano	Texas
United States	Pocatello Women's Health Clinic	Pocatello	Idaho
United States	Portneuf Medical Center	Pocatello	Idaho
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Johnston Willis Hospital	Richmond	Virginia
United States	The Pediatric Center	Rigby	Idaho
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Rochester Obstetrics and Gynecology	Rochester	New York
United States	Ascension Seton Williamson	Round Rock	Texas
United States	Baer Pediatrics	Saint Louis	Missouri
United States	KDB Enterprises	Saint Louis	Missouri
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	Sundance Clinical Research, LLC	Saint Louis	Missouri
United States	JBR Clinical Research	Salt Lake City	Utah
United States	Old Farm Obstetrics & Gynecology, LLC	Salt Lake City	Utah
United States	St. Marks Hospital	Salt Lake City	Utah
United States	Coastal Pediatric Research	Summerville	South Carolina
United States	Lowcountry Womens Specialists	Summerville	South Carolina
United States	Summerville Medical Center	Summerville	South Carolina
United States	Mesquite Pediatrics	Tucson	Arizona
United States	Watching Over Mothers and Babies	Tucson	Arizona
United States	Methodist West Hospital	West Des Moines	Iowa
United States	The Iowa Clinic	West Des Moines	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  New Zealand,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Maternal Participants With Prespecified Local Reactions by Maximum Severity Within 7 Days After Vaccination	Local reactions included pain at injection site, redness and swelling and were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (>) 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm and severe: >10.0 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity and severe: prevented daily activity. The maximum severity was defined as highest grading of each local reaction within 7 days of vaccination.	Within 7 days after vaccination
Primary	Percentage of Maternal Participants With Prespecified Systemic Events by Maximum Severity Within 7 Days After Vaccination	Systemic events included fever, fatigue, headache, nausea, muscle pain, joint pain, vomiting, diarrhea and were recorded by participants in an e-diary. Fever was categorized as: grade 1: mild (>=38.0 to 38.4 degrees [deg] Celsius [C]), grade 2: moderate (>38.4 to 38.9 deg C), grade 3: severe (>38.9 to 40.0 deg C) and grade 4 (>40.0 deg C). Fatigue, headache, nausea, muscle pain and joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: >2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. The maximum severity was defined as highest grading of each systemic event within 7 days of vaccination.	Within 7 days after vaccination
Primary	Percentage of Maternal Participants With Adverse Events (AEs) Within 1 Month After Vaccination	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect.	Within 1 month after vaccination
Primary	Percentage of Maternal Participants With Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAEs) and Obstetric Complications	MAE was defined as a non-serious AE that results in an evaluation at a medical facility. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. Obstetric complications were determined as per the study clinician's judgement.	From day of vaccination (Day 1) up to 12 months post-delivery
Primary	Percentage of Infant Participants With Specific Birth Complications	Specific birth complications included clavicle fracture, torticollis, cephalhematoma, premature baby, acute respiratory failure, meconium aspiration syndrome, neonatal pneumothorax, neonatal respiratory depression, neonatal respiratory distress, neonatal respiratory distress syndrome, neonatal respiratory failure, pneumothorax, respiratory distress, transient tachypnea of the newborn and subgaleal hemorrhage. Percentage of participants with any specific birth complications were reported in this outcome measure.	At birth
Primary	Percentage of Infant Participants With Any AE Within 1 Month of Age	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. AEs included both serious and non-serious adverse events. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect.	Within 1 month after birth
Primary	Percentage of Infant Participants With MAEs and SAEs Within 12 Months of Age	MAE was defined as a non-serious AE that results in an evaluation at a medical facility. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect.	Within 12 months after birth
Primary	Percentage of Infant Participants With AEs of Special Interest of at Least Moderate Severity Within 12 Months of Age: Congenital Anomalies and Developmental Delay	AEs of special interest for infant participants included congenital anomalies and developmental delays. Congenital anomalies were defined as structural or functional anomalies that occurred during intrauterine life and could be identified prenatally, at birth or later in life. Severity was assessed based on the study investigator's judgement and graded as grade 1= mild (does not interfere with participant's usual function); grade 2= moderate (interferes to some extent with participant's usual function); grade 3= severe (interferes significantly with participant's usual function) and grade 4= life-threatening (life-threatening consequences; urgent intervention indicated). Percentage of infant participants with AEs of special interest of at least moderate severity were presented.	Within 12 months after birth
Secondary	Geometric Mean Titer (GMT) of Respiratory Syncytial Virus Subgroup A (RSV A) and Subgroup B (RSV B) Neutralizing Antibodies in Maternal Participants	GMT of the 50% RSV A and RSV B neutralizing antibody were calculated by exponentiating the mean logarithm of the titers and the corresponding 95% confidence interval (CI) was based on the Student t distribution. Geometric mean ratios (GMRs) of the RSV vaccine group to the placebo group for the RSV A and RSV B neutralizing antibody titers at each time point was calculated and reported in statistical analysis.	Before vaccination, 2 weeks and 1 month after vaccination and at delivery
Secondary	Geometric Mean Fold Rise (GMFR) for Respiratory Syncytial Virus Subgroup A (RSV A) and Subgroup B (RSV B) Neutralizing Antibody Titers in Maternal Participants	GMFRs for RSV A and RSV B neutralizing antibody titers from before vaccination to each available time point after vaccination were calculated by exponentiating the mean logarithm of the fold rises. Corresponding 95% CI was based on the Student t distribution. Data for this outcome measure was planned to be analyzed for maternal participants only.	2 weeks and 1 month after vaccination, at delivery
Secondary	Geometric Mean Titer (GMT) of Respiratory Syncytial Virus Subgroup A (RSV A) and Subgroup B (RSV B) Neutralizing Antibodies in Infant Participants	GMT of the 50% RSV A and RSV B neutralizing antibody were calculated by exponentiating the mean logarithm of the titers and the corresponding 95% CI was based on the Student t distribution. GMRs of the RSV vaccine group to the placebo group for the RSV A and RSV B neutralizing antibody titers at each time point was calculated and reported in statistical analysis.	At birth and at 1, 2, 4, 6 months after birth

External Links

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