Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (RSV LID cp ΔM2-2) in RSV-Seronegative Infants and Children 6 to 24 Months of Age

NCT02948127 | Terminated Phase 1 DMC

• 1 other identifier: CIR 312
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the safety, infectivity, and immunogenicity of a single dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants and children 6 to 24 months of age. This study is a companion study to IMPAACT 2012.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (9)

• Grades of study product-related solicited adverse events (AEs)

  Measured through Day 28

• Grades of study product-related unsolicited AEs

  Measured through Day 28

• Grades of study product-related serious adverse events (SAEs)

  Measured through Day 56

• Number of participants with infection with vaccine virus

  Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) greater than or equal to 4-fold rise in RSV neutralizing antibody titer from Study Day 0-56

  Measured through Day 56

• Peak titer of vaccine virus shed

  Measured through Day 28

• Duration of vaccine virus shedding in nasal washes measured by culture

  Measured through Day 28

• Duration of vaccine virus shedding in nasal washes measured by RT-PCR

  Measured through Day 28

• Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer

  Measured through Day 56

• Antibody responses to RSV F glycoprotein as assessed by enzyme-linked immunosorbent assay (ELISA)

  Measured through Day 56

Secondary Outcomes (3)

• Frequency of symptomatic, medically attended respiratory and febrile illness in the vaccine and placebo recipients who experience natural infection with wild-type RSV during the subsequent RSV season

  Measured through participant's last study visit, up to a total of 6 to 12 months after study entry depending on when participants enroll in the study

• Measurement of antibody responses in the vaccine and placebo recipients who experience natural infection with wt RSV during the subsequent RSV season

  Measured at participant's last study visit, up to a total of 6 to 13 months after study entry depending on when participants enroll in the study

• Frequency of B cell responses to vaccine

  Measured through participant's last study visit, up to a total of 6 to 13 months after study entry depending on when participants enroll in the study

Study Arms (2)

RSV LID cp ΔM2-2 Vaccine

EXPERIMENTAL

Participants will receive a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0).

Biological: RSV LID cp ΔM2-2 Vaccine

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo at study entry (Day 0).

Biological: Placebo

Interventions

RSV LID cp ΔM2-2 Vaccine BIOLOGICAL

10\^5 plaque-forming units (PFUs); administered as nose drops

RSV LID cp ΔM2-2 Vaccine

Placebo BIOLOGICAL

Administered as nose drops

Placebo

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Greater than or equal to 6 months (greater than or equal to 180 days) of age at the time of screening and less than 25 months (less than 750 days) of age
• Participant is in good health based on review of the medical record, history, and physical examination, without evidence of chronic disease
• Parents/guardians are willing and able to provide written informed consent
• Seronegative for 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
• Is growing at a normal velocity for age as demonstrated on a standard growth chart 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
• Participant has received routine immunizations appropriate for age (as per Center for Disease Control Advisory Committee on Immunization Practices \[ACIP\])
• Participant is expected to be available for the duration of the study

You may not qualify if:

• Known or suspected HIV infection or impairment of immunological functions
• Bone marrow/solid organ transplant recipient
• Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities
• Previous receipt of a licensed or investigational RSV vaccine or receipt of placebo in any IMPAACT RSV study or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV Ig or RSV mAb)
• Previous anaphylactic reaction
• Previous vaccine-associated adverse reaction that was Grade 3 or above
• 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 documented 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 who is, or is scheduled to be, enrolled in CIR 311, 312 or 313 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

Sponsors & Collaborators

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

Study Sites (3)

Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

Center for Immunization Research East, Johns Hopkins Bayview Medical Center Campus

Baltimore, Maryland, 21224, United States

Location

Center for Immunization Research South

Laurel, Maryland, 20708, United States

Location

Related Publications (1)

• Cunningham CK, Karron R, Muresan P, McFarland EJ, Perlowski C, Libous J, Thumar B, Gnanashanmugam D, Moye J Jr, Schappell E, Barr E, Rexroad V, Aziz M, Deville J, Rutstein R, Yang L, Luongo C, Collins P, Buchholz U; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2012 Study Team. Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated. Open Forum Infect Dis. 2019 May 6;6(6):ofz212. doi: 10.1093/ofid/ofz212. eCollection 2019 Jun.

  PMID: 31211158 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Ruth Karron, MD

  Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: October 28, 2016
• Study Start: September 1, 2016
• Primary Completion: April 30, 2017
• Study Completion: April 30, 2018
• Last Updated: August 17, 2018

Record last verified: 2018-08

Locations

US (3)