Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine in RSV-Seronegative Infants 6 to 24 Months of Age

NCT02794870 | Completed Phase 1 Results DMC

• 2 other identifiers: IMPAACT 201130072
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study was 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 6 to 24 months of age. This study was a companion study to CIR 311.

Conditions

Respiratory Syncytial Virus Infections

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Solicited Adverse Events (AEs) by Grade

  Solicited adverse events included fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI). The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 4 and Table 5 in the protocol document.

  Measured from Day 0 through Day 28

• Number of Participants With Unsolicited AEs by Grade

  Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each unsolicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. AE grading (Grade 1- mild to Grade 4-life-threatening) was done by DAIDS AE Grading table v2.0 (see References).

  Measured from Day 0 through Day 28

• Number of Participants With Serious Adverse Events (SAEs)

  A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: * Results in death during the period of protocol-defined surveillance * Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe * Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting * Results in a persistent or significant disability/incapacity * Is a congenital anomaly or birth defect * Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

  Measured from Day 0 through Day 56

• Number of Participants Infected With RSV Vaccine

  Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) or 2) greater than or equal to 4-fold rise in serum RSV-neutralizing antibody titer between Study Days 0 and 56.

  Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28 for nasal washes, and at Days 0, 56 for serum RSV-neutralizing antibodies

• Peak Titer of Vaccine Virus Shed

  This is the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included.

  Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28

• Duration of Virus Shedding in Nasal Washes

  Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)

  Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28. Last day positive is reported.

• Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer

  Immunogenicity was assessed pre-inoculation, and at approximately 2 months post-inoculation (Study Day 56). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.

  Measured at Day 0 and Day 56

• Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

  Immunogenicity was assessed at approximately 2 months post-inoculation (Study Day 56).

  Measured at Day 56

Secondary Outcomes (3)

• Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season

  Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study

• Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season.

  Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enrolled in the study

• Number of Participants With B Cell Responses to Vaccine

  Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enrolled in the study

Study Arms (2)

RSV LID ΔM2-2 1030s vaccine

EXPERIMENTAL

Participants received a single dose of the RSV LID ΔM2-2 1030s vaccine at study entry (Day 0).

Biological: RSV LID ΔM2-2 1030s vaccine

Placebo

PLACEBO COMPARATOR

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

Biological: Placebo

Interventions

RSV LID ΔM2-2 1030s vaccine BIOLOGICAL

10\^5.0 PFU; administered as nose drops

RSV LID ΔM2-2 1030s vaccine

Placebo BIOLOGICAL

Isotonic diluent, 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 (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.
• Good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.
• Parents/guardians willing and able to provide written informed consent as described in the protocol.
• 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.
• Growing at a normal velocity for age (as demonstrated on a standard growth chart) AND
• If less than 1 year of age: current height and weight above the 5th percentile
• If 1 year of age or older: current height and weight above the 3rd percentile for age.
• Received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices \[ACIP\]).
• Expected to be available for the duration of the study.
• If born to an HIV-infected woman, participant must not have been breastfed and must have had documentation of 2 negative HIV nucleic acid (RNA or DNA) test results from samples collected on different dates with both collected when greater than or equal to 1 month of age and at least one collected when greater than or equal to 4 months of age, and no positive HIV nucleic acid (RNA or DNA) test; or 2 negative HIV antibody tests, both from samples collected at greater than or equal to 6 months of age.

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 placebo in the IMPAACT 2011 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 contained, or would 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 IMPAACT 2011, 2012 or 2013 AND there had been or would 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 was greater than or equal to 6 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count less than 300 cells/mm\^3. CD4 T lymphocyte count must have been measured within 6 months prior to enrollment, or
• a person age 1 year up to less than 6 years with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 25 or CD4 T lymphocyte count less than 750 cells/mm\^3 (if both values are available, use the lower of the two). CD4 T lymphocyte parameter must have been measured within the 6 months prior to enrollment; or
• a person age less than 1 year with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 30 or CD4 T lymphocyte count less than 1000 cells/mm\^3 (if both values are available, use the lower of the two). CD4 T lymphocyte parameter must have been measured within the 6 months prior to enrollment; or

Sponsors & Collaborators

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

Study Sites (8)

University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program

La Jolla, California, 92093-0672, United States

Location

Usc La Nichd Crs

Los Angeles, California, 90089, United States

Location

Univ. of Colorado Denver NICHD CRS

Aurora, Colorado, 80045, United States

Location

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, 60612, United States

Location

Lurie Children's Hospital of Chicago (LCH) CRS

Chicago, Illinois, 60614-3393, United States

Location

Johns Hopkins University Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794-8111, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

Related Links

• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Results Point of Contact

• Title: Melissa Allen, Director, IMPAACT Operations Center
• Organization: Family Health International (FHI 360)

mallen@fhi360.org

(919) 405-1429

Study Officials

• Elizabeth J. McFarland, MD

  Children's Hospital Colorado Pediatric Infectious Diseases

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 24, 2016
• First Posted: June 9, 2016
• Study Start: July 15, 2016
• Primary Completion: July 7, 2017
• Study Completion: July 7, 2017
• Last Updated: August 27, 2018
• Results First Posted: August 27, 2018

Record last verified: 2018-07

Locations

US (8)