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Challenge Infection of Healthy Adult Volunteers With RSV A2

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ClinicalTrials.gov Identifier: NCT03388645
Recruitment Status : Recruiting
First Posted : January 3, 2018
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date  ICMJE December 30, 2017
First Posted Date  ICMJE January 3, 2018
Last Update Posted Date March 25, 2019
Actual Study Start Date  ICMJE February 20, 2018
Estimated Primary Completion Date November 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2019)
  • Assessment of expected and unexpected adverse events after challenge [ Time Frame: Safety will be assessed continuously during the inpatient phase and at Day 28 and 56 during the outpatient phase of the study. ]
    Characterize the onset, duration, and magnitude of viral shedding after RSV A2 challenge infection.
  • Detect RSV shedding in nasopharyngeal wash by FilmArray multiplex pCR assay and by quantitative RT-PCR and quantitative viral culture after challenge with RSV A2 [ Time Frame: Beginning with study Day 2 on a daily basis during the inpatient phase ]
    Determine the safety and infectability of high dose, recombinant RSV A2 administered by nasal atomizer to healthy adult volunteers
Original Primary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • Assessment of expected and unexpected adverse events after challenge [ Time Frame: Safety will be assessed continuously during the inpatient phase and at Day 28 and 56 during the outpatient phase of the study. ]
  • Detect RSV shedding in nasopharyngeal wash by FilmArray multiplex pCR assay and by quantitative RT-PCR and quantitative viral culture after challenge with RSV A2 [ Time Frame: Beginning with study Day 2 on a daily basis during the inpatient phase ]
Change History Complete list of historical versions of study NCT03388645 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2018)
  • Calculate the number participants with mild to moderate upper respiratory illness after challenge, based on stdy definition of RSV illness and determine the no. of days RSV illness persists after challenge and degree of illness based on stdy def... [ Time Frame: Clinical signs and symptoms will be assessed daily during inpatient phase. ]
  • Determine the frequency, magnitude, and duration of serum and mucosal (nasopharyngeal wash) RSV-specific antibody responses after challenge. [ Time Frame: Serum for neutralizing antibody titer(PRNT), anti-RSV IgG, anti-F and/or anti-G will occur on Day, -1, Day 28, and Day 56. NP wash or nasosorption for immunoglobulins (eg secretory IgA) will occur on D-1, Day7, Day 10, Day 28, and Day 56. ]
  • Determine day of onset of shedding, no. of days of shedding, peak nasal wash viral titer, and mean sum of daily virus titers after challenge and correlate the magnitude and duration of viral shedding with the severity and duration of RSV-related... [ Time Frame: RSV shedding will be assessed on a daily basis beginning with study Day 2 during the inpatient phase through the day of discharge. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Challenge Infection of Healthy Adult Volunteers With RSV A2
Official Title  ICMJE Challenge Infection of Healthy Adult Volunteers With RSV A2
Brief Summary

Background:

One of the main causes of respiratory infections in children and adults is RSV. This stands for respiratory syncytial virus. Healthy adults usually get a cold when they get an infection with RSV. They generally recover without any problems. But some infections can be life-threatening. Researchers want to study RSV infection in a safe, controlled setting in healthy adults to help develop new treatments.

Objective:

To test the safety of a higher dose of RSV A2 by spraying the virus into the nose, and studying how the body responds.

Eligibility:

Healthy adults ages 18-50

Design:

Participants will be screened during 2 screening visits with:

  • Medical interview
  • Physical exam
  • Blood and nasal samples
  • Chest X-ray (chest radiograph)
  • Participants will have a heart test. Sticky patches on the body will detect heart electrical activity.
  • Pulmonary function test (PFT). They will blow into a machine to measure airflow.
  • Urine tests for pregnancy or drug use.

Participants will be admitted to the hospital before they get RSV A2.

Participants will get a single dose of RSV A2 as two sprays, one into each nostril.

Participants will stay in the hospital under isolation for as long as it takes the body to clear RSV A2 from nasal fluids. This can take as long as 14 days or more.

Participants cannot take any cold medicine to try to feel better.

Every day, participants will:

  • Answer questions about their symptoms
  • Have nasal washes and/or nasal swabs collected
  • Have a quick physical exam

Participants will have blood drawn most days.

After discharge, participants will keep a health diary.

Participants will have 2 follow-up visits over 2 months. They will repeat most of the screening procedures.

Detailed Description

Respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infection. RSV also causes lower respiratory tract disease in the elderly and life-threatening disease in immunocompromised hosts. An RSV monoclonal antibody (palivizumab) is currently available for passive immunoprophylaxis in high-risk infants. Vaccines and antiviral agents are under development for the treatment and prevention of RSV, but none are licensed. The ability to challenge healthy volunteers with RSV could rapidly facilitate efficacy studies of future antivirals and vaccines. In addition, challenge studies would provide critical information on viral pathogenesis, including types of cells infected, mucosal and systemic immune response, and alterations in respiratory microbiota. Clinical trial material for human challenge studies has been prepared from live recombinant (complementary DNA-derived) RSV of subgroup A (RSV A2).

This study will be a phase 1 study in healthy adult male and non-pregnant female subjects 18 years to 50 years of age. The main purpose of the trial is to define the safety profile, determine the frequency of RSV shedding in nasal wash, estimate RSV illness rates, and study immune responses in subjects given 1 dose of 10^7 PFU of RSV A2 challenge virus using a nasal atomizer. If RSV A2 is found to be sufficiently infectious in adults, then it may be used as a challenge virus in future studies evaluating antivirals or the protective efficacy of RSV vaccines, or in studies of the immunopathogenesis of RSV infection.

Subjects will be admitted to the NIH Clinical Center and receive a single intranasal dose of 10^6.3 PFU or 107 PFU of RSV A2. Subjects will remain at the Clinical Center for approximately 9-14 days after challenge infection undergoing sequential clinical evaluations. Research specimens, nasal washes and blood, will be collected for various research assays. Subjects will be discharged when their daily nasal wash RSV result is negative for two days in a row, and they do not have any signs or symptoms suggestive of possible RSV-associated lower respiratory tract disease. Subjects will return for follow-up evaluation 28 and 56 days after viral challenge.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Upper Respiratory Tract Infections
Intervention  ICMJE Biological: RSV A2
Each adult volunteer will receive a single intranasal inoculation of RSV A2 administered with a nasal atomizer with subsequent sampling of nasal fluids and blood draws.
Study Arms  ICMJE
  • Experimental: 1-Low Dose RSV challenge
    The first four volunteers will receive a dose of 10^3PFU of RSV A2. This will be followed by daily clinical assessments and collection of nasal fluid and blood samples for virologic and immunologic assays. Subjects will have 2 follow-up outpatient visits at Day 28 and 56. Intervention: Single intranasal dose of 10^6.3 PFU of RSV A2 using a nasal atomizer on Day 0
    Intervention: Biological: RSV A2
  • Experimental: 2-4 - High Dose RSV A2
    The volunteers for the following 3 cohorts of 7 volunteers will receive 10 PFU of RSV A2. This will be followed by daily clinical assessments and collection of nasal fluid and blood samples for virologic and immunologic assays. Subjects will have 2 follow-up outpatient visits at Day 28 and 56. Intervention: Single intranasal dose of RSV A2 at 10^7 PFU using a nasal atomizer on Day 0.
    Intervention: Biological: RSV A2
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 2, 2018)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2019
Estimated Primary Completion Date November 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

    1. Age 18-50 years inclusive.
    2. General good health, without significant medical illness, physical exam findings, or significant laboratory abnormalities as determined by the investigator.
    3. Willingness to stay confined to the inpatient unit for required study duration.
    4. Willingness to have samples stored for future research.
    5. Subjects must be of non-childbearing potential (e.g., surgically sterilized (bilateral oophorectomy, bilateral tubal ligation, hysterectomy)) or, if of child-bearing potential and sexually active with a partner who can get them pregnant, must have in place an effective method of contraception for at least 30 days prior to administration of the challenge virus and until 30 days after challenge virus

      administration:

      • intrauterine device (IUD) or equivalent
      • hormonal contraceptives (e.g., consistent, continuous use of contraceptive pill, patch, ring, implant, or injection)

        ---if participant uses contraceptive pill, patch, or ring, they must also use a barrier method at the time of potentially reproductive sexual activity (e.g., (male/female condom, cap, or diaphragm) plus spermicide)

      • be in a monogamous relationship with a partner who has undergone a vasectomy at least 180 days prior to first dose of study agent
    6. A plaque reduction RSV neutralization titer < 8.0 log(2).

EXCLUSION CRITERIA:

  1. Subject who was previously challenged with RSV A2.
  2. Female subject who is pregnant or lactating OR planning to become pregnant from 30 days prior to inoculation through 30 days after inoculation.
  3. Presence of self-reported or medically documented significant medical condition(s) including but not limited to:

    -Respiratory disease (e.g., chronic obstructive pulmonary disease, emphysema, rhinitis, sinusitis) in adulthood, and additionally:

    --A history of asthma within the past 5 years, or a current diagnosis of asthma or reactive airway disease associated with

    exercise, seasonal hay fever or allergic rhinitis

    --Presence of any febrile illness or symptoms suggestive of a respiratory infection within 2 weeks prior to inoculation.

    • Any significant abnormality of the nose or nasopharynx, including recurrent epistaxis within 90 days prior to viral inoculation or nasal or sinus surgery within 180 days prior to viral inoculation.
    • Chronic cardiovascular disease (e.g., congenstive heart failure, cardiomyopathy, ischemic heart disease).
    • Chronic neurological or neurodevelopmental conditions (e.g., cerebral palsy, epilepsty, stroke, seizures).
    • Ongoing malignancy.
    • Chronic medical condition requiring close medical follow-up or hospitalization during the past 5 years (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathy, autoimmune disease).
    • An immunodeficiency.
  4. Use of systemic corticosteroids exceeding 10 mg/day of prednisone equivalent and nasal steroid preparations or immunosuppressive drugs within 30 days before inoculation and within 60 days after. Low dose topical steroid preparations used for a discrete period of time are permitted.
  5. Inhaled bronchodilator or inhaled steroid use within the last 360 days or use after upper respiratory tract infections.
  6. Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol.
  7. Complete blood count (CBC), AST, ALT, creatinine values or other screening labs or tests (e.g. electrocardiogram (EKG), chest x-ray (CXR)) are outside of the NIH Department of Laboratory Medicine normal reference range and deemed clinically significant by the PI.
  8. Positive FDA-approved HIV test obtained during screening procedures.
  9. Positive serology for hepatitis C virus obtained during screening period.
  10. Presence of hepatitis B surface antigen obtained during screening period.
  11. A smoker of tobacco products or a routine marijuana smoker currently or in the past year.
  12. Current alcohol abuse or addiction.
  13. Current illicit drug abuse or addiction.
  14. Receipt of a licensed vaccine within 30 days prior to RSV A2 inoculation and planned vaccination within 60 days after inoculation..
  15. Receipt of blood or blood-derived products (including immunoglobulin) within 180 days prior to viral inoculation. Receipt of packed red blood cells given for an emergent indication in an otherwise healthy person, and not required as ongoing treatment, is not exclusionary.
  16. Receipt of an investigational agent or vaccine within 90 days prior to scheduled RSV A2 inoculation and planned receipt within 60 days after inoculation.
  17. A body mass index (BMI) less than or equal to 18.5 or greater than or equal to 37.0.
  18. A medical, occupational, or family problem that would preclude the participant from complying with all study requirements.
  19. Shares household, works closely with, or has routine contact with a child (children) < 5 years of age or with immunocompromised individual(s), adult(s) with significant cardiopulmonary disease or asthma, institutionalized persons or persons with functional disability, or any other individual that, in the judgment of the PI, might be at increased risk for complications if exposed to RSV.
  20. Deprived of freedom by an administrative or court order or in an emergency setting.
  21. Any condition that in the opinion of the PI would jeopardize the safety or rights of a person participating in the trial or would render the person unable to comply with the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Krista S Gangler, R.N. (301) 761-6437 krista.gangler@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03388645
Other Study ID Numbers  ICMJE 180039
18-I-0039
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lesia K Dropulic, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 15, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP