RSV F Vaccine Maternal Immunization Study in Healthy Third-trimester Pregnant Women.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of an RSV-F protein nanoparticle vaccine, with aluminum, in healthy third-trimester pregnant women and to assess the impact of maternal immunization on infant safety through one year of life.

Official Title
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A Phase II Randomized, Observer-Blind, Placebo-Controlled, Study to Evaluate the Safety and Immunogenicity of a Respiratory Syncytial Virus (RSV) F Nanoparticle Vaccine With Aluminum, in Healthy Third-trimester Pregnant Women and to Assess the Impact of Maternal Immunization on Infant Safety Through One Year of Life

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: Saline Placebo (0.5mL injection)
* Drug: RSV F vaccine (0.5mL injection)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women must meet all of the following criteria to be eligible to participate: ≥18 and ≤40 years-of-age. Singleton pregnancy of 33 to 35 weeks gestation on the day of planned vaccination. Good general maternal health as demonstrated by: Medical history (including history of adverse reactions to prior vaccines and allergies). Physical examination including at least vital signs (blood pressure, pulse, respirations, and oral temperature); weight; height; examination of the HEENT, cardiovascular, pulmonary, gastrointestinal (abdominal), musculoskeletal, lymphatic, and dermatologic organ systems; and documentation of fetal heart tones. Clinical laboratory parameters including normal blood urea nitrogen, creatinine, ALT, AST, total bilirubin, alkaline phosphatase (ALP), hemoglobin, white blood count, and platelet count; and serologic exclusion of infection with hepatitis B (HBV) and C (HCV) viruses and HIV (as required). Note that normal ranges for vital signs and clinical laboratory parameters will be based on third trimester values published in Sheffield et al. [2013] and/or reference ranges for the third trimester of pregnancy of the central laboratory. Documentation that fulfills one of the following: Detailed (level II) second trimester or later anatomic ultrasound with no significant anatomic or growth abnormalities identified; OR Routine second trimester or later ultrasound with no significant anatomic or growth abnormalities identified, PLUS at least one of the following: Normal first trimester screening (based on ultrasound + serum analytes); or Normal cell-free fetal DNA; or Normal chorionic villus sampling (CVS) or amniocentesis; or Normal second trimester maternal serum quadruple screen; or Normal first and second trimester screening using integrated, sequential, or contingency approach; or Abnormal first or second trimester screening followed by normal CVS, amniocentesis, or cell-free fetal DNA. Able to understand, and both willing and physically able to comply with study procedures. This includes anticipation of reasonable geographic proximity to the study clinic and adequate transportation to comply with scheduled and unscheduled study follow-up visits. Able and willing to provide written informed consent for themselves and infant. Exclusion Criteria: Pregnant women will be excluded if there is historical, physical examination, or laboratory evidence of any of the following criteria: Symptomatic cardiac or pulmonary disease requiring chronic drug therapy, including hypertension and asthma. Asthma will be exclusionary if the subject is receiving chronic systemic glucocorticoids at any dose or inhaled glucocorticoids at any dose >500µg per day of beclamethasone or fluticasone, or >800μg per day of budesonide. Pre-pregnancy body mass index (BMI) of ≥35 or <18.5. Hemoglobinopathy (including known sickle trait or thalassemias, even if asymptomatic) or blood dyscrasias. Hepatic or renal dysfunction. Established diagnosis of seizure disorder, regardless of therapy. Auto-immune disease or known immunodeficiency syndrome. Endocrine disorders, including (but not limited to) hyperthyroidism, untreated hypothyroidism, and glucose intolerance (e.g., diabetes mellitus type 1 or 2) antedating pregnancy, or occurring during pregnancy and requiring interventions other than diet for control. History of major gynecologic or major abdominal surgery, including bariatric surgery. Known HIV, HBV, or HCV infection, as assessed by serologic tests conducted during the current pregnancy or as a procedure during the screening period of the study. Primary genital herpes simplex (HSV) infection during the current pregnancy. Current alcohol or drug abuse. Documentation that current pregnancy results from fertility treatments, rape, or incest. Documentation that the infant will be a ward of the state or be released for adoption. Neuro-psychiatric illness deemed likely to interfere with protocol compliance, safety reporting, or receipt of pre-natal care; or requiring treatment with psychotropic drugs. History/presence of deep venous thrombosis or thromboembolism, or the use of anticoagulants during pregnancy. Untreated red blood cell allo-immunization. Prior stillbirth or neonatal death, or multiple (≥3) spontaneous abortions. Prior preterm delivery ≤34 weeks gestation or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm birth. Greater than five (5) prior deliveries. Previous infant with a known genetic disorder or major congenital anomaly. Receipt of investigational drugs or immune globulins (with the exception of prophylactic anti-Rho D immune globulin) within six (6) months prior to the administration of the study vaccine. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted except for the limit established in exclusion criterion #1. Any other physical, psychiatric or social condition which may, in the investigator's opinion, increase the risks of study participation to the maternal subject or the fetus/infant; or may lead to the collection of incomplete or inaccurate safety data.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Treatment Group A<br>Saline Placebo (0.5mL injection) | Drug: Saline Placebo (0.5mL injection)<br> <br> * Other names: 0.9% Sodium Choloride;|
| Experimental: Treatment Group B<br>RSV F vaccine with adjuvant (0.5mL injection) | Drug: RSV F vaccine (0.5mL injection)<br> <br> * Other names: RSV F Protein with Aluminum adjuvant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Counts and percentage of subjects with solicited injection site and systemic reactogenicity within seven days of vaccination. | In Maternal Subjects | Day 0 to Day D+180 | 
| Counts and percentage of subjects with unsolicited (local and systemic) adverse events (AE), unscheduled medically-attended adverse events (MAEs), and serious adverse events (SAEs) through delivery and six (6) months thereafter. | In Maternal Subjects | Day 0 to Day D+180 | 
| Clinical safety laboratory assessments of select serum chemistry and hematology parameters through delivery. | In Maternal Subjects | Screening to Day 14 | 
| Counts and percentage of subjects with post-immunization onset of specific complications of third-trimester pregnancy and delivery | In Maternal Subjects | Day 0 to Day 28 - 42 | 
| Counts and percentage of term healthy infants appropriate for gestational age. | In Infant subjects | Day 28 - 42 | 
| Neonatal SAEs (including congenital anomalies, respiratory failure, fever/infection, and neonatal death or other adverse events/complications that necessitate extended hospitalization). | In Infant Subjects | Birth to Day 365 | 
| Growth and development over one year | In Infant Subjects | Birth to Day Day 365 | 
| Counts and proportion of infants with unsolicited adverse events | In Infant Subjects | Birth to Day 365 | 
| Counts and proportions of infants with medically-attended RSV lower respiratory tract infection (LRTI), and age of onset of those infections. | In Infant Subjects | Birth to Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity as assessed by serum IgG antibody titers specific fro the F-Protein antigen. | In Infant Subjects | Birth to Day 180 | 
| Serum antibody titers inhibiting binding of labeled palivizumab to RSV F protein. | In Infant Subjects | Birth to Day 180 | 
| Serum microneutralization (MN) titers against RSV/A and B.previously referenced, but based on GMT. | In Infant Subjects | Birth to Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV, Third Trimester, Maternal Immunization