Evaluating the Infectivity, Safety, and Immunogenicity of the Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants and Children 6 to 24 Months of Age

Respiratory Syncytial Virus Infections Clinical Trial

Official title:

Randomized Phase I Study of the Infectivity, Safety, and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 or Placebo, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03422237
• Other study ID #: CIR 321
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: October 4, 2017
• Est. completion date: September 20, 2020

Study information

• Verified date: March 2020
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of the recombinant live-attenuated respiratory syncytial virus (RSV) vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 or placebo when delivered as nose drops to RSV-seronegative infants and children 6 to 24 months of age.

This study is a companion study to IMPAACT 2018.

Description:

Human respiratory syncytial virus (RSV) is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age worldwide. This study will evaluate the infectivity, safety, and immunogenicity of two recombinant live-attenuated RSV vaccines: RSV ΔNS2/Δ1313/I1314L and RSV 276. The vaccines will be delivered as nose drops to RSV-seronegative infants and children 6 to 24 months of age.

Participants will be randomly assigned to receive a single dose of the RSV ΔNS2/Δ1313/I1314L vaccine, the RSV 276 vaccine, or placebo at study entry (Day 0).

Participants will be enrolled in the study outside of RSV season, i.e., between April 1 and October 31. All participants will remain on study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration is between 6 and 13 months, depending on when they enroll in the study.

Participants will attend several study visits throughout the study, which may include physical examinations, blood collection, nasal washes, and nasal adsorption (nasosorption) specimen collection. Participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: September 20, 2020
• Est. primary completion date: September 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 24 Months

Eligibility

Inclusion Criteria:

• Greater than or equal to 6 months (defined as greater than or equal to 180 days) of age at the time of screening and less than 25 months (defined as less than 750 days) of age at the time of enrollment

• In good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.

• Parent/guardian is willing and able to provide written informed consent as described in the protocol.

• Seronegative for respiratory syncytial virus (RSV) antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening from a sample collected no more than 42 days prior to inoculation. Note: results from specimens collected during screening for any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (NIAID, NIH) are acceptable as long as within the 42-day window.

• Growing normally for age (i.e., not downwardly crossing two major centiles on a standard growth chart) in the six months prior to enrollment AND

• If less than 1 year of age: has a current height and weight above the 5th percentile

• If 1 year of age or older: has a current height and weight above the 3rd percentile for age.

• Has received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices [ACIP]). Note: if rotavirus immunization was delayed, "catch-up" rotavirus immunization is indicated only if the participant is age-eligible per ACIP.

• Is expected to be available for the duration of the study.

Exclusion Criteria:

• Known or suspected HIV infection or impairment of immunological functions.

• Receipt of immunosuppressive therapy, including any systemic, including either nasal or inhaled, corticosteroids within 28 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.

• Any receipt of bone marrow/solid organ transplant.

• Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities.

• Previous receipt of a licensed or investigational RSV vaccine (or placebo in any International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) RSV study) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG or RSV mAb).

• Any previous anaphylactic reaction.

• Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if grading is not possible, determine if the reaction was considered severe or life threatening; if so, it is exclusionary.

• Any known hypersensitivity to any study product component.

• Heart disease. Note: Participants with cardiac abnormalities documented to be clinically insignificant and requiring no treatment may be enrolled.

• Lung disease, including any history of reactive airway disease or medically diagnosed wheezing.

• Member of a household that contains, or will contain, an infant who is less than 6 months of age at the enrollment date through Day 28.

• Member of a household that contains another child/other children who is/are, or is/are scheduled to be, enrolled in IMPAACT 2018 AND the date of enrollment to IMPAACT 2018 will not be concurrent with the other participant(s) living in the household (i.e., all eligible children from the same household must be enrolled on the same date).

• Member of a household that contains another child who is, or is scheduled to be, enrolled in another study evaluating an intranasal live-attenuated RSV vaccine, AND there has been or will be an overlap in residency during that other child's participation in the study's Acute Phase (Days 0 to 28).

• Member of a household that contains an immunocompromised individual, including, but not limited to:

• a person who is HIV infected

• a person who has received chemotherapy within the 12 months prior to enrollment

• a person receiving immunosuppressant agents

• a person living with a solid organ or bone marrow transplant.

• Attends a daycare facility and shares a room with infants less than 6 months of age, and parent/guardian is unable or unwilling to suspend daycare for 28 days following inoculation.

• Any of the following events at the time of enrollment:

• fever (temporal or rectal temperature of greater than or equal to 100.4 degrees F), or

• upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or

• nasal congestion significant enough to interfere with successful inoculation, or

• otitis media.

• Receipt of the following prior to enrollment:

• any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or

• any live vaccine, other than rotavirus vaccine, within the 28 days prior, or

• another investigational vaccine or investigational drug within 28 days prior

• Scheduled administration of the following after planned inoculation:

• inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or

• any live vaccine other than rotavirus in the 28 days after, or

• another investigational vaccine or investigational drug in the 56 days after

• Receipt of immunoglobulin, any antibody products, or any blood products within the past 6 months prior to enrollment

• Receipt of any of the following medications within 3 days prior to study enrollment:

• systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or

• intranasal medications, or

• other prescription medication except as listed below. Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.

• Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days prior to enrollment.

• Born at less than 34 weeks gestation.

• Born at less than 37 weeks gestation and less than 1 year of age at the time of enrollment.

• Current suspected or documented developmental disorder, delay, or other developmental problem.

• Any previous receipt of supplemental oxygen therapy in a home setting.

Related Conditions & MeSH terms

• Respiratory Syncytial Virus Infections
• Virus Diseases

Intervention

Biological:
• RSV ?NS2/?1313/I1314L
10^6 plaque-forming units (PFU); administered as nose drops
• RSV 276
10^5 PFU; administered as nose drops
• Placebo
Administered as nose drops

Locations

Country	Name	City	State
United States	Center for Immunization Research East, Johns Hopkins Bayview Medical Center Campus	Baltimore	Maryland
United States	Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health	Baltimore	Maryland
United States	Center for Immunization Research South	Laurel	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grades of study product-related solicited adverse events (AEs)	May include fever, acute otitis media, upper respiratory tract illness (URI), or lower respiratory tract illness (LRI)	Measured through Day 28
Primary	Grades of study product-related unsolicited AEs	Defined as all other AEs that are not solicited AEs	Measured through Day 28
Primary	Grades of study product-related serious adverse events (SAEs)	SAEs as defined in the protocol	Measured through Day 56
Primary	Number of participants infected with RSV	Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes done throughout this time period; Day 0 nasal wash will be counted as baseline) and/or 2) greater than or equal to 4-fold rise in RSV serum neutralizing antibody titer and/or serum enzyme-linked immunosorbent assay (ELISA) titer to the RSV F protein from study entry to Study Day 56	Measured through Day 56
Primary	Peak titer of vaccine virus shed	Determined from virologic assays	Measured through Day 28
Primary	Duration of virus shedding in nasal washes	As determined by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)	Measured through Day 28
Primary	Frequency of a greater than or equal to 4-fold rise in RSV serum neutralizing antibody titer	Determined from virologic and immunologic assays	Measured through Day 56
Primary	Frequency of RSV neutralizing antibody responses	Assessed by 60% RSV plaque reduction neutralization assay at study entry and Study Day 56	Measured through Day 56
Primary	Frequency of a greater than or equal to 4-fold rise in serum antibody titers to RSV F glycoprotein	Assessed by ELISA	Measured through Day 56
Primary	Frequency of antibody responses to RSV F glycoprotein	Assessed by ELISA	Measured through Day 56
Secondary	Frequency of symptomatic, medically attended respiratory and febrile illness AEs in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season	Illness graded by severity based on clinical assessments	Measured through Month 13
Secondary	Frequency of antibody responses in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season	Determined from virologic and immunologic assays	Measured through Month 13
Secondary	Frequency of B cell response to vaccine	Determined from virologic and immunologic assays	Measured through Month 13
Secondary	Frequency of mucosal antibody responses to vaccine	Determined from nasal wash or nasosorption samples	Measured through Month 13