Safety Study of Respiratory Syncytial Virus (RSV)-Fusion (F) Protein Particle Vaccine
Primary Purpose
Respiratory Syncytial Virus Infections
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RSV-F Particle Vaccine
RSV-F Particle Vaccine
RSV-F Particle Vaccine
RSV-F Particle Vaccine
Placebo
RSV-F Particle Vaccine
RSV-F Particle Vaccine
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Syncytial Virus Infections focused on measuring RSV
Eligibility Criteria
Inclusion Criteria:
- Male or female aged 18 to 49 years inclusive
- Ability to provide written informed consent to participate
- Healthy, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations at baseline
Females are required to fulfill one of the following criteria:
- At least 1 year post-menopausal
- Surgically sterile
- Willing to use oral, implantable, transdermal or injectable contraceptives for 30 days prior to first vaccination and until 28 days after each vaccination
- Willing to abstain from sexual intercourse or use another reliable form of contraception approved by the Investigator (eg, intrauterine device, female condom, and diaphragm with spermicide, cervical cap, use of condom by the sexual partner, or a sterile sexual partner) for study duration and until 28 days after vaccination
- All female subjects must have a negative urine pregnancy test within 48 hours preceding receipt of each vaccination.
- Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits and be contacted by telephone throughout the follow-up period
Exclusion Criteria:
- Presence of significant uncontrolled medical or psychiatric illness (acute or chronic). This includes institution of new medical or surgical treatment, or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed on Day 1 prior to vaccination
- Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies
- Pregnant or lactating female
- Females who plan to become pregnant or plan to discontinue contraceptive precautions within 30 days prior to first vaccination and 28 days after each vaccination
- Cancer, or treatment for cancer, within 3 years, excluding basal cell carcinoma or squamous cell carcinoma, which is allowed
- Presence of any medical condition that may be associated with impaired immune responsiveness, including diabetes mellitus
- Receipt (or history of receipt), during the preceding 3-month period, of any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable). Inhaled and topical corticosteroids will be allowed.
- Receipt or planned administration of a nonstudy vaccine within 30 days prior to vaccination or during the study. If a nonstudy vaccine has been administered, administration of study vaccine injection can be delayed and given as soon as allowable within the 30-day window, provided the nonstudy vaccine is not administered within 2 weeks prior to study enrollment. Immunization with Tetanus Toxoids Adsorbed for adult use (Td or Tdap) vaccine, on an emergency basis, up to 8 days before or at least 8 days after a dose of study vaccine will be allowed.
- History of illicit drug or alcohol abuse within the previous 1 year or positive drug or alcohol screen
- History of anaphylactic type reaction to injected vaccines
- Receipt of any investigational product or nonregistered drug within the 30 days prior to vaccination or current enrollment in any investigational drug study or intent to enroll in such a study within the ensuing study period
- Receipt or donation of blood or blood products 8 weeks prior to vaccination or planned receipt or donation during the study period
- Acute disease, defined as the presence of a moderate or severe illness (as determined by the Investigator through medical history and physical examination) with or without fever, or an oral temperature of ≥38ºC, within 72 hours prior to vaccination. Study vaccine can be administered to persons with a minor illness, such as diarrhea or mild upper respiratory tract infection with or without low-grade fever. Vaccination can be delayed until the subject has recovered.
- Any condition that, in the opinion of the Investigator, would interfere with the primary study objectives
Sites / Locations
- Healthcare Discoveries d/b/a ICON Development Solutions
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Arm Label
A: Dose 1 + adjuvant
B: Dose 2 + adjuvant
C: Dose 3 + adjuvant
D: Dose 3 alone
E: Placebo control
F: Dose 4 alone
G: Dose 4 +adjuvant
Arm Description
Outcomes
Primary Outcome Measures
To assess and compare the safety, reactogenicity, and tolerability of 6 RSV-F protein particle vaccine formulations.
This primary outcome will be evaluated through an assessment of the following parameters:
Immediate AEs
Solicited AEs
All SAEs and SNMCs
Vital signs
Laboratory Assessments
Secondary Outcome Measures
To assess and compare the immunogenicity (neutralizing antibody and total anti-F antibody) of the 6 RSV-F protein particle vaccine formulations
This secondary outcome will be assessed in the following manner:
Neutralizing antibody against RSV measured in a PRNT assay
Total anti-F IgG measured by ELISA by ELISA
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01290419
Brief Title
Safety Study of Respiratory Syncytial Virus (RSV)-Fusion (F) Protein Particle Vaccine
Official Title
A Phase 1 Randomized, Observer-Blinded,Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of a Recombinant Respiratory Syncytial Virus F Protein Particle Vaccine in Healthy Adults
Study Type
Interventional
2. Study Status
Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novavax
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Phase 1, Randomized, Placebo-Controlled, Observer-Blinded, Escalating Dose-Ranging Study to Assess the Safety, and immunogenicity of 6 different recombinant RSV-F formulations in healthy adults (18 to 49 years of age).
Study Objectives:
Primary:
To assess and compare the safety, reactogenicity, and tolerability of 6 RSV-F protein particle vaccine formulations.
Secondary:
To assess and compare the immunogenicity (neutralizing antibody and total anti-F antibody) of the 6 RSV-F protein particle vaccine formulations
To confirm the "dose sparing" and "value added" effects of the aluminum phosphate adjuvant
Detailed Description
A total of 150 subjects will be allocated to 7 cohorts. Subjects will be randomly assigned to vaccine treatment or saline placebo in a 4:1 ratio, such that each cohort will include 20 subjects who receive active vaccine (Groups A, B, C, D, F and G) and 5 subjects who receive placebo (Group E).
Subjects will be followed for all AEs, including SAEs and non-serious AEs, from the time of each vaccination through 30 days following the second vaccination (Day 60±5). After Day 60, subjects will be contacted via telephone on a monthly basis (approximately Days 90, 120, 150, 180, and 210) and asked about the occurrence of SAEs and SNMCs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Syncytial Virus Infections
Keywords
RSV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A: Dose 1 + adjuvant
Arm Type
Experimental
Arm Title
B: Dose 2 + adjuvant
Arm Type
Experimental
Arm Title
C: Dose 3 + adjuvant
Arm Type
Experimental
Arm Title
D: Dose 3 alone
Arm Type
Experimental
Arm Title
E: Placebo control
Arm Type
Placebo Comparator
Arm Title
F: Dose 4 alone
Arm Type
Experimental
Arm Title
G: Dose 4 +adjuvant
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
RSV-F Particle Vaccine
Intervention Description
Dose 1 + adjuvant / dose; Day 0 and Day 30
Intervention Type
Biological
Intervention Name(s)
RSV-F Particle Vaccine
Intervention Description
Dose 2 + adjuvant / dose; Day 0 and Day 30
Intervention Type
Biological
Intervention Name(s)
RSV-F Particle Vaccine
Intervention Description
Dose 3 + adjuvant / dose; Day 0 and Day 30
Intervention Type
Biological
Intervention Name(s)
RSV-F Particle Vaccine
Intervention Description
Dose 3 / dose; Day 0 and Day 30
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo; Day 0 and Day 30
Intervention Type
Biological
Intervention Name(s)
RSV-F Particle Vaccine
Intervention Description
Dose 4 / dose; Day 0 and Day 30
Intervention Type
Biological
Intervention Name(s)
RSV-F Particle Vaccine
Intervention Description
Dose 4 + adjuvant / dose; Day 0 and Day 30
Primary Outcome Measure Information:
Title
To assess and compare the safety, reactogenicity, and tolerability of 6 RSV-F protein particle vaccine formulations.
Description
This primary outcome will be evaluated through an assessment of the following parameters:
Immediate AEs
Solicited AEs
All SAEs and SNMCs
Vital signs
Laboratory Assessments
Time Frame
Day 60 (2 months)
Secondary Outcome Measure Information:
Title
To assess and compare the immunogenicity (neutralizing antibody and total anti-F antibody) of the 6 RSV-F protein particle vaccine formulations
Description
This secondary outcome will be assessed in the following manner:
Neutralizing antibody against RSV measured in a PRNT assay
Total anti-F IgG measured by ELISA by ELISA
Time Frame
Day 60 (2 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female aged 18 to 49 years inclusive
Ability to provide written informed consent to participate
Healthy, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations at baseline
Females are required to fulfill one of the following criteria:
At least 1 year post-menopausal
Surgically sterile
Willing to use oral, implantable, transdermal or injectable contraceptives for 30 days prior to first vaccination and until 28 days after each vaccination
Willing to abstain from sexual intercourse or use another reliable form of contraception approved by the Investigator (eg, intrauterine device, female condom, and diaphragm with spermicide, cervical cap, use of condom by the sexual partner, or a sterile sexual partner) for study duration and until 28 days after vaccination
All female subjects must have a negative urine pregnancy test within 48 hours preceding receipt of each vaccination.
Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits and be contacted by telephone throughout the follow-up period
Exclusion Criteria:
Presence of significant uncontrolled medical or psychiatric illness (acute or chronic). This includes institution of new medical or surgical treatment, or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening and reconfirmed on Day 1 prior to vaccination
Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies
Pregnant or lactating female
Females who plan to become pregnant or plan to discontinue contraceptive precautions within 30 days prior to first vaccination and 28 days after each vaccination
Cancer, or treatment for cancer, within 3 years, excluding basal cell carcinoma or squamous cell carcinoma, which is allowed
Presence of any medical condition that may be associated with impaired immune responsiveness, including diabetes mellitus
Receipt (or history of receipt), during the preceding 3-month period, of any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable). Inhaled and topical corticosteroids will be allowed.
Receipt or planned administration of a nonstudy vaccine within 30 days prior to vaccination or during the study. If a nonstudy vaccine has been administered, administration of study vaccine injection can be delayed and given as soon as allowable within the 30-day window, provided the nonstudy vaccine is not administered within 2 weeks prior to study enrollment. Immunization with Tetanus Toxoids Adsorbed for adult use (Td or Tdap) vaccine, on an emergency basis, up to 8 days before or at least 8 days after a dose of study vaccine will be allowed.
History of illicit drug or alcohol abuse within the previous 1 year or positive drug or alcohol screen
History of anaphylactic type reaction to injected vaccines
Receipt of any investigational product or nonregistered drug within the 30 days prior to vaccination or current enrollment in any investigational drug study or intent to enroll in such a study within the ensuing study period
Receipt or donation of blood or blood products 8 weeks prior to vaccination or planned receipt or donation during the study period
Acute disease, defined as the presence of a moderate or severe illness (as determined by the Investigator through medical history and physical examination) with or without fever, or an oral temperature of ≥38ºC, within 72 hours prior to vaccination. Study vaccine can be administered to persons with a minor illness, such as diarrhea or mild upper respiratory tract infection with or without low-grade fever. Vaccination can be delayed until the subject has recovered.
Any condition that, in the opinion of the Investigator, would interfere with the primary study objectives
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
D. Nigel Thomas, Ph.D.
Organizational Affiliation
Novavax, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Dennis Ruff, MD
Organizational Affiliation
Healthcare Discoveries d/b/a ICON Development Solutions
Official's Role
Principal Investigator
Facility Information:
Facility Name
Healthcare Discoveries d/b/a ICON Development Solutions
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
10814577
Citation
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Results Reference
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PubMed Identifier
1765771
Citation
Collins PL, Mottet G. Post-translational processing and oligomerization of the fusion glycoprotein of human respiratory syncytial virus. J Gen Virol. 1991 Dec;72 ( Pt 12):3095-101. doi: 10.1099/0022-1317-72-12-3095.
Results Reference
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PubMed Identifier
9359721
Citation
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Results Reference
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PubMed Identifier
9658147
Citation
Lopez JA, Bustos R, Orvell C, Berois M, Arbiza J, Garcia-Barreno B, Melero JA. Antigenic structure of human respiratory syncytial virus fusion glycoprotein. J Virol. 1998 Aug;72(8):6922-8. doi: 10.1128/JVI.72.8.6922-6928.1998.
Results Reference
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PubMed Identifier
9349459
Citation
Melero JA, Garcia-Barreno B, Martinez I, Pringle CR, Cane PA. Antigenic structure, evolution and immunobiology of human respiratory syncytial virus attachment (G) protein. J Gen Virol. 1997 Oct;78 ( Pt 10):2411-8. doi: 10.1099/0022-1317-78-10-2411. No abstract available.
Results Reference
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PubMed Identifier
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Citation
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.
Results Reference
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U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. September 2007.
Results Reference
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Glenn GM, Smith G, Fries L, Raghunandan R, Lu H, Zhou B, Thomas DN, Hickman SP, Kpamegan E, Boddapati S, Piedra PA. Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine. Vaccine. 2013 Jan 7;31(3):524-32. doi: 10.1016/j.vaccine.2012.11.009. Epub 2012 Nov 12.
Results Reference
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Safety Study of Respiratory Syncytial Virus (RSV)-Fusion (F) Protein Particle Vaccine
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