A Safety and Immunogenicity Study of Intranasal Sendai Virus Vectored Respiratory Syncytial Virus (SeVRSV) Vaccine in Healthy Adults

NCT ID: NCT03473002

Last Updated: 2019-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-16
• Study Completion Date: 2019-02-14

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.

Conditions

Antiviral Prophylaxis; Respiratory Syncytial Virus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Placebo

One dose of placebo (0.9% Sodium Chloride) intranasally, n=4

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

0.9% Sodium Chloride

SeVRSV

1 x 10\^7 EID50 (one dose) of SeVRSV vaccine intranasally, n=16

Group Type: EXPERIMENTAL

SeVRSV Vaccine

Intervention Type: BIOLOGICAL

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.

Interventions

Placebo

0.9% Sodium Chloride

Intervention Type: OTHER

SeVRSV 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

Exclusion Criteria

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.

1. Have an acute illness, as determined by the site PI or appropriate sub-investigator, within 72 hours prior to study vaccination.

• An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol. Subjects may re-screen after an acute illness is resolved.

2. Have any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation.

-- Including acute or chronic medical disease or condition, defined as persisting for at least 90 days, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study.

3. History of anatomic disorder of the nares or nasopharynx (Deviated septum is allowed).

4. History of chronic sinus infections.

5. A diagnosis of type I or II diabetes.

6. Have a body mass index (BMI) < 18.5 or > / = 35 kg/m^2.

7. History of medical diagnosis of selected respiratory diseases.

--- Asthma as an adult (defined as diagnosis at > / = 18 years of age), reactive airway disease, wheezing requiring medication as an adult (defined as diagnosis at > / = 18 years of age), cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically confirmed apnea, hospitalization for respiratory illness or mechanical ventilation for respiratory illness.

8. History of smoking in the last 5 years.

9. Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.

10. Have known active neoplastic disease or a history of any hematologic malignancy. Non-melanoma skin cancers that are not active are permitted.

11. Positive hepatitis C, or HIV serology or positive hepatitis B serology not consistent with prior hepatitis B immunization.

12. History of Bell's Palsy.

13. History of anosmia (per subject report of ever having symptoms or clinician diagnosis).

14. Have known hypersensitivity or allergy to eggs, or other components of the study vaccine.

15. Have a history of alcohol or drug abuse within 5 years prior to study vaccination.

16. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.

17. Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 10 years prior to study vaccination.

18. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose within 30 days prior to study vaccination.

19. Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination.

---- High-dose defined using the inhaled high-dose reference chart.

20. Receipt of any intranasal medication within 7 days prior to study vaccination through 14 days post study vaccination.

21. Received any licensed live vaccine within 30 days of study vaccination.

22. Received a licensed inactivated vaccine within 14 days of the study vaccination.

23. Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination.

24. Received an experimental agent within 28 days prior to study vaccination, or expects to receive an experimental agent during the 6-month trial-reporting period.

----- Including vaccine, drug, biologic, device, blood product, or medication.

------ Other than from participation in this study.

25. Female subjects who are breastfeeding or plan to breastfeed at any given time from the receipt of study vaccination throughout the 6 month trial period.

26. Expected household contact or same room contact for > 1 hour with children < 6 months of age or immunocompromised individuals within 7 days of receipt of study vaccination.

27. Day care provider or healthcare provider with direct contact with children or patients.

28. Have received any antiviral drug within 3 days of study vaccination.

29. Any condition that would, in the opinion of the Site Investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

HHSN272201300016I

Identifier Type: -

Identifier Source: secondary_id

16-0108

Identifier Type: -

Identifier Source: org_study_id