RSV F Dose-Ranging Study in Women

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of multiple formulations of an RSV-F protein nanoparticle vaccine, with aluminum, in healthy women of child-bearing age.

Official Title
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A Phase II Randomized, Observer-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Immunogenicity and Safety of Multiple Formulations of an RSV F Particle Vaccine With Aluminum, in Healthy Women of Child-Bearing Age

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Biological: Low dose RSV F Antigen
* Biological: High dose RSV F Antigen
* Biological: Dose 1 of Aluminum Adjuvant
* Biological: Dose 2 of Aluminum Adjuvant
* Biological: Dose 3 of Aluminum Adjuvant
* Biological: Dose 4 of Aluminum Adjuvant
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet the following criteria to be eligible to participate: Healthy adult females, ≥ 18 and ≤ 35 years of age. Healthy shall be defined by the absence of any illness, acute or chronic, that requires ongoing systemic therapy for the control of symptoms or prevention of disability. Subjects on stable (no change in ≥ 3 months) therapy for findings (e.g., hypertension or hyperlipidemia) that are not associated with symptoms or disability are eligible, as are users of hormonal contraceptives. Subjects who receive intermittent prophylaxis for risks associated with asymptomatic findings (e.g., antibiotic prophylaxis prior to dental procedures in a subject with mitral valve prolapse) are eligible. Ongoing therapy will be defined as continuous or, if intermittent, more frequent than once every 3 months (e.g., use of an inhaled bronchodilator for exercise-induced bronchospasm more than once every 3 months). Immunosuppressives are subject to exclusion criterion #5 below. Persons being treated for illnesses or conditions that would become acutely symptomatic or disabling in the absence of treatment are not eligible. Willing and able to give informed consent prior to study enrollment. Able to comply with study requirements. Women who are not surgically sterile must have a negative urine pregnancy test prior to each vaccination; will be advised through the Informed Consent process to avoid becoming pregnant over the duration of the study, and must assert that they will employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: credible history of continuous abstinence from heterosexual activity, hormonal contraceptives (oral, injectable, implant, patch, ring), double-barrier contraceptives (condom or diaphragm, with spermicide), and IUD. Exclusion Criteria: Subjects will be excluded if they fulfill any of the following criteria: Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first vaccination. History of a serious reaction to any prior vaccination. Received any vaccine in the 4 weeks preceding the study vaccination; or any RSV vaccine at any time. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination. 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. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study. Donated blood within 3 weeks of the planned date of first vaccination. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature >38.0°C on the planned day of vaccine administration). Known disturbance of coagulation. Women who are pregnant or breastfeeding, or plan to become pregnant during the study. Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse. Any condition that in the opinion of the Investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose RSV F Vaccine with Dose 1 of Aluminum Adjuvant<br>Day 0: Low dose RSV F Antigen with Dose 1 of aluminum adjuvant Day 28: Placebo | Biological: Low dose RSV F Antigen<br> <br> Biological: Dose 1 of Aluminum Adjuvant<br> <br> Biological: Placebo<br> <br> |
| Experimental: Low dose RSV F Vaccine with Dose 2 of Aluminum Adjuvant<br>Day 0: Low dose RSV F Antigen content with Dose 2 of aluminum adjuvant Day 28: Low dose RSV F Antigen content with Dose 2 of aluminum adjuvant | Biological: Low dose RSV F Antigen<br> <br> Biological: Dose 2 of Aluminum Adjuvant<br> <br> |
| Experimental: Low dose RSV F Vaccine with Dose 3 of Aluminum Adjuvant<br>Day 0: Low dose RSV F Antigen with Dose 3 of aluminum adjuvant Day 28: Low dose RSV F Antigen with Dose 3 of aluminum adjuvant | Biological: Low dose RSV F Antigen<br> <br> Biological: Dose 3 of Aluminum Adjuvant<br> <br> |
| Experimental: Low dose RSV F Vaccine with Dose 4 of Aluminum Adjuvant<br>Day 0: Low dose RSV F Antigen with Dose 4 of aluminum adjuvant Day 28: Low dose RSV F Antigen with Dose 4 of aluminum adjuvant | Biological: Low dose RSV F Antigen<br> <br> Biological: Dose 4 of Aluminum Adjuvant<br> <br> |
| Experimental: High dose RSV F Vaccine with Dose 2 of Aluminum Adjuvant<br>Day 0: High dose RSV F Antigen with Dose 2 of aluminum adjuvant Day 28: Placebo | Biological: High dose RSV F Antigen<br> <br> Biological: Dose 2 of Aluminum Adjuvant<br> <br> Biological: Placebo<br> <br> |
| Experimental: High dose RSV F Vaccine with Dose 3 of Aluminum Adjuvant<br>Day 0: High dose RSV F Antigen with Dose 3 of aluminum adjuvant Day 28: Placebo | Biological: High dose RSV F Antigen<br> <br> Biological: Dose 3 of Aluminum Adjuvant<br> <br> Biological: Placebo<br> <br> |
| Experimental: High dose RSV F Vaccine with Dose 4 of Aluminum Adjuvant<br>Day 0: High dose RSV F Antigen content with Dose 4 of aluminum adjuvant Day 28: Placebo | Biological: High dose RSV F Antigen<br> <br> Biological: Dose 4 of Aluminum Adjuvant<br> <br> Biological: Placebo<br> <br> |
| Placebo Comparator: Placebo<br>Day 0: Placebo Day 28: Placebo | Biological: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity as assessed by serum IgG antibody titers specific for the F-Protein antigen across treatment groups | Serum IgG antibody concentrations as ELISA units (EUs) specific for the F protein antigen. Derived/calculated endpoints based on these data will include: Geometric mean concentrations as EU (GMEU) Geometric mean ratio (GMR) Geometric mean fold-rise (GMFR) Seroconversion rate (SCR) Seroresponse rate (SRR) | Day 0 to Day 56 | 
| Assessment of Safety | Numbers and percentages of subjects with solicited local and systemic adverse events over the seven days post-injection; and all adverse events, solicited and unsolicited, including adverse changes in clinical laboratory parameters. In addition, Medically Attended Events, Serious Adverse Events, and Significant New Medical Conditions will be collected for six months. | Day 0 to Day 182 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity based on neutralizing antibody titer |  | Day 0 to Day 56 | 
| Kinetics of serum IgG antibody titers specific for the F-Protein antigen across time |  | Day 0 to Day 91 | 
| Immunogenicity based on antibodies sharing specificity with Palivizumab |  | Day 0 to 91 |