Challenge Infection of Healthy Adult Volunteers With RSV A2

NCT03388645 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 18003918-I-0039
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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 high 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 physical exam Participants will have blood drawn most days. After discharge, participants will keep a health diary. Participants will have 2 follow-up visits at 1 month and 2 months after receiving the RSV A2 dose. A history and physical examination, a blood draw, and nasal wash and swab will be performed.

Conditions

Upper Respiratory Tract Infections

Keywords

RSV Shedding; Immune Responses; Neutralizing Antibody Titer; Upper Respiratory Tract Infection

Outcome Measures

Primary Outcomes (5)

• Participants With Detectable RSV Shedding in Nasopharyngeal Wash

  Participants who had shedding of RSV as assessed by detection of RSV A2 in nasal wash by FilmArray multiplex polymerase chain reaction (PCR), by reverse transcriptase (RT)-quantitative PCR, or by quantitative viral culture.

  Daily from study Day 2 through day 10 after challenge with RSV A2

• Participants With Related, Expected Adverse Events After Challenge

  Participants who had one or more episodes of related, expected adverse events. Participants were evaluated for grades 1 to 3 adverse events. Only grade 1 adverse events were experienced.

  Safety assessed continuously during the inpatient phase and at Day 28 and 56 during the outpatient phase of the study

• Participants With Unrelated Expected Adverse Events After Challenge

  Participants who had one or more episodes of unrelated, expected adverse events. Participants were evaluated for grades 1 to 3 adverse events. Only grade 1 adverse events were experienced.

  Safety assessed continuously during the inpatient phase and at Day 28 and 56 during the outpatient phase of the study

• Participants With Related, Unexpected Adverse Events After Challenge

  Participants who had one or more episodes of related, unexpected adverse events. Related, unexpected adverse events are those that are not expected but are related to RSV A2 or of grade 4 severity and related to RSV A2. Only grade 1 adverse events were experienced.

  Safety assessed continuously during the inpatient phase and at Day 28 and 56 during the outpatient phase of the study

• Participants With Unrelated, Unexpected Adverse Events After Challenge

  Participants who had one or more episodes of unrelated, unexpected adverse events. Unrelated, unexpected adverse events are those that are not expected and are not related to RSV A2.

  Safety assessed continuously during the inpatient phase and at Day 28 and 56 during the outpatient phase of the study

Secondary Outcomes (1)

• Participants With Mild to Moderate Upper Respiratory Illness

  Daily from study Day 2 through day 10 after RSV challenge

Study Arms (2)

Low Dose 10^6.3 PFU of RSV A2

EXPERIMENTAL

Single intranasal dose of 10\^6.3 plaque forming units (PFU) of respiratory syncytial virus A2 (RSV A2) using a nasal atomizer on Day 0

Biological: 10^6.3 PFU of RSV A2

High Dose 10^7 PFU of RSV A2

EXPERIMENTAL

Single intranasal dose of 10\^7 plaque forming units (PFU) of respiratory syncytial virus A2 (RSV A2) using a nasal atomizer on Day 0

Biological: 10^7 PFU of RSV A2

Interventions

10^6.3 PFU of RSV A2 BIOLOGICAL

Each adult volunteer will receive a single intranasal inoculation of 10\^6.3 PFU of RSV A2 administered with a nasal atomizer with subsequent sampling of nasal fluids and blood draws.

Low Dose 10^6.3 PFU of RSV A2

10^7 PFU of RSV A2 BIOLOGICAL

Each adult volunteer will receive a single intranasal inoculation of 10\^7 PFU of RSV A2 administered with a nasal atomizer with subsequent sampling of nasal fluids and blood draws.

High Dose 10^7 PFU of RSV A2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50 years inclusive.
• General good health, without significant medical illness, physical exam findings, or significant laboratory abnormalities as determined by the investigator.
• Willingness to stay confined to the inpatient unit for required study duration.
• Willingness to have samples stored for future research.
• 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
• A plaque reduction RSV neutralization titer \< 8.0 log(2).

You may not qualify if:

• Subject who was previously challenged with RSV A2.
• Female subject who is pregnant or lactating OR planning to become pregnant from 30 days prior to inoculation through 30 days after inoculation.
• 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., congestive heart failure, cardiomyopathy, ischemic heart disease).
• Chronic neurological or neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, 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.
• 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.
• Inhaled bronchodilator or inhaled steroid use within the last 360 days or use after upper respiratory tract infections.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• DeVincenzo JP, Whitley RJ, Mackman RL, Scaglioni-Weinlich C, Harrison L, Farrell E, McBride S, Lambkin-Williams R, Jordan R, Xin Y, Ramanathan S, O'Riordan T, Lewis SA, Li X, Toback SL, Lin SL, Chien JW. Oral GS-5806 activity in a respiratory syncytial virus challenge study. N Engl J Med. 2014 Aug 21;371(8):711-22. doi: 10.1056/NEJMoa1401184.

  PMID: 25140957 BACKGROUND

• Hall CB, Long CE, Schnabel KC. Respiratory syncytial virus infections in previously healthy working adults. Clin Infect Dis. 2001 Sep 15;33(6):792-6. doi: 10.1086/322657. Epub 2001 Aug 21.

  PMID: 11512084 BACKGROUND

• Lee FE, Walsh EE, Falsey AR, Betts RF, Treanor JJ. Experimental infection of humans with A2 respiratory syncytial virus. Antiviral Res. 2004 Sep;63(3):191-6. doi: 10.1016/j.antiviral.2004.04.005.

  PMID: 15451187 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Lesia Dropulic
• Organization: National Institute of Allergy and Infectious Diseases

dropulicl@niaid.nih.gov

+1 301 496 7675

Study Officials

• Lesia K Dropulic, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2017
• First Posted: January 3, 2018
• Study Start: February 20, 2018
• Primary Completion: November 15, 2019
• Study Completion: December 6, 2019
• Last Updated: December 3, 2020
• Results First Posted: December 3, 2020

Record last verified: 2019-12-06

Locations

US (1)