Antiviral Prophylaxis, Respiratory Syncytial Virus Infection
Conditions
Keywords
Immunogenicity, Respiratory Syncytial Virus, Safety, Sendai Virus, Vaccine
Brief summary
This is a Phase I randomized, double blind, placebo controlled trial in up to 25 males and non-pregnant females, 18-45 years old, inclusive, who are in good health and meet all eligibility criteria. This trial is designed to assess the safety, reactogenicity and immunogenicity of a single intranasal dose of Sendai virus vectored Respiratory Syncytial Virus (SeVRSV) vaccine. The subjects will be randomized in a 4:1 ratio to receive SeVRSV vaccine at a dose of 1 x 10\^7 EID50 or placebo (saline) intranasally. Study duration is approximately 11 months with subject participation duration approximately 6 months. The primary objectives are to: 1) assess the safety and reactogenicity of SeVRSV vaccine following receipt of one intranasal dose; 2) assess the ELISA antibody responses to SeV and to the RSV F protein at 28 days post receipt of one intranasal dose of SeVRSV vaccine; 3) assess the detection of vaccine virus from nasal washes at days 3, 5, 8 and 15 following receipt of one intranasal dose of SeVRSV vaccine.
Detailed description
This is a Phase I randomized, double blind, placebo controlled trial in up to 25 males and non-pregnant females, 18-45 years old, inclusive, who are in good health and meet all eligibility criteria. This trial is designed to assess the safety, reactogenicity and immunogenicity of a single intranasal dose of Sendai virus vectored Respiratory Syncytial Virus (SeVRSV) vaccine. The subjects will be randomly assigned in a 4:1 ratio to receive SeVRSV vaccine at a dose of 1 x 10\^7 EID50 or placebo (saline) intranasally. Since this is a first in human, phase I study, the first two subjects (sentinels) will be enrolled in the SeVRSV treatment arm. Safety and laboratory data will be collected through 14 days post vaccination. If none of the predefined halting criteria of sentinel subjects are met, enrollment of the remaining subjects will proceed. If any of the pre-defined halting criteria of sentinel subjects are met, an electronic review by the SMC will be required prior to continuation of the study. While safety is evaluated for the sentinel subjects, no new subjects will be enrolled, but screening may continue. Study duration is approximately 11 months with subject participation duration approximately 6 months. The primary objectives are to: 1) assess the safety and reactogenicity of SeVRSV vaccine following receipt of one intranasal dose; 2) assess the ELISA antibody responses to SeV and to the RSV F protein at 28 days post receipt of one intranasal dose of SeVRSV vaccine; 3) assess the detection of vaccine virus from nasal washes at days 3, 5, 8 and 15 following receipt of one intranasal dose of SeVRSV vaccine.
Interventions
OTHERPlacebo
0.9% Sodium Chloride
BIOLOGICALSeVRSV Vaccine
Recombinant Sendai virus vectored respiratory syncytial virus (SeVRSV) vaccine. SeVRSV is a replication-competent Sendai virus that carries the RSV F gene produced by reverse genetics technology.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1\. Provide written informed consent before initiation of any study procedures. 2. Are able to understand and comply with planned study procedures and be available for all study visits/phone calls. 3\. Males or non-pregnant females 18-45, inclusive. 4. Are in good health. * As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days that would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days. This includes no change in chronic prescription medication, dose, or frequency as a result of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes subsequent to enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical, nasal, and inhaled medications (with the exception of steroids as outlined in the Subject
Exclusion criteria
), herbals, vitamins, and supplements are permitted. 5\. Oral temperature is less than 100.0 degrees Fahrenheit. 6. Pulse is 47 to 105 beats per minute (bpm), inclusive. 7. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive. 8. Diastolic blood pressure (BP) is 55 to 95 mmHg, inclusive. 9. Women of childbearing potential must use an acceptable method of contraception from 30 days prior to study vaccination until 60 days after study vaccination. * Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure (R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or \< 1 year of the last menses if menopausal. \--- Includes, but is not limited to, non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, NuvaRing (R), and licensed hormonal methods such as implants, injectables or oral contraceptives (the pill). 10\. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to study vaccination. 11\. Sexually active males with a woman of childbearing potential and has not had a vasectomy performed \> 1 year prior to screening must agree not to father a child for 60 days after vaccination. * See criteria of women of childbearing potential above. ----- Must agree to use a barrier method of birth control e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner uses occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. 11\. Erythrocyte sedimentation rate (ESR) is less than 30 mm per hour. 12. White blood cells (WBC) are greater than 4.4 x 10\^3/uL and less than 11.1 x 10\^3/uL. 13\. Hemoglobin (Hgb) is greater than 11.6 g/dL for females or is greater than 13.2 g/dL for males. 14\. Platelets are greater than 134 x 10\^3/uL and less than 466 x 10\^3/uL. 15. Absolute Neutrophil Count is greater than 1.7 x 10\^3/uL \------ For subjects who are of African American or Middle Eastern decent, ANC must be greater than 0.8 x 10\^3/uL for inclusion. 16\. Alanine aminotransferase (ALT) is less than 1.25 ULN for females and males. 17. Aspartate aminotransferase (AST) is less than 1.25 ULN for females and males. 18\. Total bilirubin is less than 1.11 mg/dL. 19. Creatinine is less than 0.96 mg/dL for females or is less than 1.18 mg/dL for males. 20\. Sodium is greater than 135 mmol/L and less than 146 mmol/L. 21. Potassium is greater than 3.4 mmol/L and less than 5.2 mmol/L. 22. BUN is less than 19 mg/dL (BUN will be obtained only if creatinine is above normal range). 23\. HgbA1C is less than 6.3%. 24. Have normal screening laboratories for urine protein. Trace protein is acceptable. 25\. Drug screen for opiates is negative. 26. Have a normal ECG. * Abnormal screening electrocardiogram (ECG) defined as pathologic Q waves and significant ST-T wave changes: criteria for left ventricular hypertrophy; and any non-sinus rhythm excluding isolated premature atrial contractions. 27\. Agrees not to participate in another clinical trial during the study period. 28\. Agrees not to donate blood or blood products to a blood bank for 6 months after receiving the vaccine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of clinical safety laboratory abnormalities | Up to 7 days |
| Occurrence of Medically Significant Wheezing | Up to 6 months |
| Occurrence of New Onset Chronic Medical Conditions (NOCMCs) | Up to 6 months |
| Occurrence of SAEs not related to study product | Up to 6 months |
| Occurrence of solicited local reactogenicity | Up to 14 days |
| Occurrence of solicited systemic reactogenicity | Up to 14 days |
| Occurrence of unsolicited adverse events | Up to day 28 |
| Occurrence of vaccine-related SAEs | Up to 6 months |
| Percentage of subjects achieving a 4 - fold rise in RSV F antibody titer measured by ELISA | From day 1 through day 29 |
| Percentage of subjects achieving a 4 - fold rise in SeV antibody titer measured by ELISA | From day 1 through day 29 |
| Percentage of subjects with vaccine virus detected by nasal wash assessed by Polymerase Chain Reaction (PCR) | Day 15 |
Countries
United States
Outcome results
None listed