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Trial record 1 of 1 for:    NCT02484417
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Respiratory Syncytial Virus Human Challenge in Healthy Adult Volunteers

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ClinicalTrials.gov Identifier: NCT02484417
Recruitment Status : Completed
First Posted : June 29, 2015
Last Update Posted : March 20, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

Background:

- Respiratory syncytial virus (RSV) can cause respiratory infections. Some of these can be life-threatening, especially in young children, the elderly, and people with weak immune systems. Researchers want to study RSV infection in a hospital setting in healthy adults. They want to use what they learn to test new treatments or vaccines in the future.

Objectives:

- To study how the body responds to RSV.

Eligibility:

- Healthy volunteers ages 18-50

Design:

  • Participants will be screened under another protocol.
  • Participants will have:
  • Medical history
  • Physical exams
  • EKG. Heart rhythm is measured with small sticky patches on the chest, arms, and legs.
  • Chest x-ray
  • Pulmonary function tests. This measures how much air a person can move into and out of the lungs.
  • Blood and urine tests
  • Nasal washes and/or nasal swabs. For the wash, the nose will be rinsed with a sterile liquid. For the swab, the inside of the nostril will be rubbed with a cotton swab.
  • Participants will have two, possibly three, follow-up outpatient visits, approximately 1, 2 and 6 months after receiving the dose of RSV.
  • Participants will stay in the hospital under isolation for 7 or more days after getting the virus.
  • The average stay is 10 days. Participants cannot leave the isolation unit. They cannot have visitors.
  • The virus should cause a mild to medium cold.
  • Participants will fill out a symptom card every day in the hospital and for 1 month after.
  • Participants will have 2 follow-up visits, 28 and 56 days after leaving the hospital.
  • Female participants who are sexually active must remain abstinent or use an effective form of birth control for 1 month before and after getting the virus.

Condition or disease Intervention/treatment Phase
Upper Respiratory Tract Infection Biological: RSV A2 Phase 1

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 purpose of the trial is to define safety profiles and estimate illness rates for subjects given 2 different doses of RSV A2 challenge virus. If RSV A2 is found to be sufficiently infectious in adults, then it may be used as a challenge virus in future studies evaluating the protective efficacy of RSV vaccines or antivirals and in studies of pathogenesis of RSV.

Subjects will be admitted to the NIH Clinical Center and receive a single intranasal dose of RSV A2 at either 10^5 or 10^6.3 PFU. Subjects will remain at the Clinical Center for approximately 9-12 days for clinical evaluation. Research procedures conducted on blood and nasal swab and wash samples will include lymphocyte phenotyping, cytokine analysis, transcriptosome profiling, RSV-specific immunoglobin analysis (circulating IgG and nasal secretory IgA), quantitative viral titers and viral culture, and nasal microbiome analysis. Subjects will be discharged when their NP wash RSV results are negative for two consecutive days and they do not have any signs or symptoms suggestive of possible RSV-associated lower respiratory tract disease. Subjects will return for followup evaluation 28 and 56 days after viral challenge.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase I Study of Respiratory Syncytial Virus Human Challenge in Healthy Adult Volunteers
Actual Study Start Date : July 21, 2015
Actual Primary Completion Date : August 10, 2016
Actual Study Completion Date : September 9, 2016

Arm Intervention/treatment
Experimental: Cohort 1: RSV A2 10^5 PFU/dose
Challenge 4 subjects with low dose and proceed to larger cohort after safety review.
Biological: RSV A2
Intranasal inoculation of healthy volunteers with 10^5 or 10^6.3 plaque forming units (PFU) of RSV A2.

Experimental: Cohort 2: RSV A2 10^5 PFU/dose
Challenge 12 subjects with the low dose and proceed to high dose after safety review.
Biological: RSV A2
Intranasal inoculation of healthy volunteers with 10^5 or 10^6.3 plaque forming units (PFU) of RSV A2.

Experimental: Cohort 3: RSV A2 10^6.3 PFU/dose
Challenge 12 subjects with the high dose
Biological: RSV A2
Intranasal inoculation of healthy volunteers with 10^5 or 10^6.3 plaque forming units (PFU) of RSV A2.




Primary Outcome Measures :
  1. Collection and assessment of expected and unexpected AEs. [ Time Frame: Safety will be assessed continuously during inpatient and outpatient phases of the study through Day 56 ]
    Safety


Secondary Outcome Measures :
  1. RSV challenge associated immune responses: neutralizing antibody and immune cell phenotyping [ Time Frame: Immune responses were assessed on Days 1, 7, and 10 during inpatient stay. Immune responsewere also examined during outpatient visits on Day 28, Day 56 and Day 180. ]
    Antibody and T cell responses

  2. RSV challenge associated viral shedding from nasal secretions: viral titer onset, duration, peak, and AUC [ Time Frame: Viral shedding was assessed daily during the inpatient phase starting on Day 2 following study virus inoculation through day of discharge. ]
    Viral shedding detected on nasal wash

  3. RSV challenge associated clinical disease: frequency of upper respiratory infection, and symptom score and mucos [ Time Frame: Clinical signs and symptoms were assessed daily during the inpatient phase. Interim history and physical was performed during outpatient visits. ]
    RSV Illness



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

    1. Age 18-50 years.
    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 (i.e., either 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, then they must be 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, two methods of contraception are required; a barrier method is to be used 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 6 months prior to first dose of study agent.

EXCLUSION CRITERIA:

The presence of any one of the following criteria is sufficient to exclude a prospective subject from enrolling in this study:

  1. Female subject is pregnant or lactating OR planning to become pregnant in the timeframe that begins 30 days prior to the inoculation and ends 30 days after inoculation.
  2. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, hematologic, rheumatologic, endocrine, autoimmune, or renal disease.
  3. Complete blood count (CBC), AST, ALT, or creatinine values are both outside of the NIH Department of Laboratory Medicine normal reference range and deemed clinically significant by the PI.
  4. 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.
  5. A medical, occupational, or family problem as a result of alcohol or illicit drug use during the past 12 months.
  6. Routine smoker of a tobacco product or marijuana currently or in the past year.
  7. Current alcohol abuse or addiction.
  8. Current illicit drug abuse or addiction.
  9. Presence of any febrile illness or symptoms suggestive of a viral respiratory infection within 2 weeks prior to inoculation accompanied by a positive multiplex FilmArray PCR performed on nasal wash.
  10. Use of corticosteroids (including nasal preparations) or immunosuppressive drugs within 30 days before inoculation.
  11. A history of asthma within the past 10 years, or a current diagnosis of asthma or reactive airway disease associated with exercise, seasonal hay fever or allergic rhinitis.
  12. Positive FDA-approved HIV test result prior to inoculation.
  13. Positive serology for hepatitis C virus within 6 months prior to inoculation.
  14. Presence of hepatitis B surface antigen within 6 months prior to inoculation.
  15. A known immunodeficiency syndrome.
  16. Receipt of a licensed vaccine within 4 weeks prior to viral inoculation.
  17. Receipt of blood or blood-derived products (including immunoglobulin) within 6 months 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 (for example packed red blood cells emergently given during an elective surgery).
  18. Receipt of another investigational agent within 3 months prior to viral inoculation.
  19. Individual with body mass index (BMI) less than or equal to 18.5 or greater than or equal to 37.5.
  20. Any significant abnormality of the nose or nasopharynx, including recurrent epistaxis within 3 months prior to viral inoculation.
  21. Nasal or sinus surgery within 6 months prior to viral inoculation.
  22. Shares household, works closely with, or has routine contact with a child (children) < 5 years of age or with immunocompromised individual(s), adults with significant cardiopulmonary disease, persons with significant asthma, institutionalized elderly or elderly 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.
  23. Deprived of freedom by an administrative or court order or in an emergency setting.
  24. Any condition that in the opinion of the principal investigator (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02484417


Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Lesia K Dropulic, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
Additional Information:
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02484417    
Other Study ID Numbers: 150148
15-I-0148
First Posted: June 29, 2015    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 17, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Neutralizing Antibody
Viral Shedding
Mucosal Immune Reponse
RSV
Healthy Volunteer
Additional relevant MeSH terms:
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Respiratory Tract Infections
Infection
Respiratory Tract Diseases