Respiratory Syncytial Virus InfectionsPhase 1NCT02237209
Safety and Immune Response to a Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children
A Phase 1 study testing RSV LID ΔM2-2 Vaccine in people with Respiratory Syncytial Virus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial summary
Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around the world. This study will evaluate the safety and immune response to an RSV vaccine in RSV-seronegative infants and children. This study is a companion study to CIR 291. Read more about this study
- Who is it for?
- Ages 6 to 24 monthsHealthy volunteers can take part
- Conditions the study is for
- Respiratory Syncytial Virus Infections
- What is being tested?
- RSV LID ΔM2-2 Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2014to Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 24 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Participant is at least 6 months (defined as at least 180 days) of age at the time of screening and less than 25 months (defined as 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. Note: any questions regarding interpretation of this criterion should be forwarded to the team.
- Parents/guardians demonstrate their understanding of the study, sign the informed consent, and agree to administration of study product following a detailed explanation of the study
- Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening obtained no more than 42 days prior to scheduled inoculation
- Has a current height and weight above the 5th percentile for age
- Participant has received routine immunizations appropriate for age. Prior vaccines were administered at least:
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- 2 weeks prior to enrollment for inactivated and subunit vaccines and rotavirus vaccine, and
- 4 weeks prior to enrollment for all other live vaccines.
- Participant is expected to be available for the duration of the study
- If born to an HIV-infected woman, participant must be non-breastfeeding with documentation of two negative HIV nucleic acid (RNA or DNA) tests with both collected when at least 1 month of age and at least one collected when at least 4 months of age, and no positive HIV nucleic acid (RNA or DNA) test; or two negative HIV antibody tests, both collected at less than or equal to 6 months of age
Who cannot join
- Known or suspected HIV infection or impairment of immunological functions
- Receipt of immunosuppressive therapy, including any systemic corticosteroids within 30 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.
- 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) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG)
- Previous vaccine-associated anaphylactic or other severe adverse vaccine reaction
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- 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 wheezing or reactive airway disease
- 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 IMPAACT 2000, 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 greater than or equal to 5 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count less than 300/mcL. CD4 T lymphocyte count must have been measured within 6 months prior to enrollment; or
- a person less than 5 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 15. CD4 T lymphocyte percentage must have been measured within the 6 months prior to enrollment; or
- a person who has received chemotherapy within the 12 months prior to enrollment.
- Verbal report of CD4 T cell lymphocyte is sufficient documentation if the parent/guardian is confident of history.
- 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 (rectal temperature of greater than or equal to 100.4°F [38°C]), 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 killed 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:
- killed vaccine within the 14 days after, or
- any live vaccine other than rotavirus in the 28 days after, or
- another investigational vaccine or drug in the 28 days after.
- Receipt of immunoglobulin, any antibody products, or any blood products
- Receipt of any of the following medications within 3 days of study enrollment:
- systemic antibacterial, antiviral, antifungal, antiparasitic, 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 past month
- Born at less than 37 weeks gestation and less than 1 year of age at the time of enrollment
- Meets criteria for failure to thrive within the 6 months prior to enrollment: a decline in height or weight growth that has crossed two major growth percentiles (e.g., from above the 75th to below the 25th) in an interval of less than 6 months
- Suspected or documented developmental disorder, delay, or other developmental problem
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Usc La Nichd Crs
Alhambra, California, 91803
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, 80045
Johns Hopkins University Center for Immunization Research
Baltimore, Maryland, 21205
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, 60612
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
University of California, UC San Diego CRS
La Jolla, California, 92093-0672
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
About this study
Official title: A Phase I Study of the Safety and Immunogenicity of Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine RSV LID ΔM2-2 in RSV-Seronegative Infants and Children
Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around the world. This study will evaluate the safety and immune response to an RSV vaccine in RSV-seronegative infants and children.
This study is a companion study to CIR 291.
Read the detailed description
RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age in the world. RSV illness can range from mild upper respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia. Severe RSV disease in infancy may also predispose children to develop reactive airway disease during childhood. The purpose of this study is to evaluate the safety and immunogenicity of an RSV vaccine (RSV LID ΔM2-2) in RSV-seronegative infants and children at least 6 months and through 24 months of age.
To determine study eligibility, the screening process will include a blood collection. Screening may begin after the RSV season (i.e., as of April 1) and enrollment must precede the RSV season (no later than October 14). At study entry, eligible participants will be randomly assigned to receive one dose of either the RSV vaccine or placebo, which will be delivered as nose drops. Participants will also undergo a review of medical history, clinical assessment, and a nasal wash. They will then receive their assigned vaccine and will remain under observation for monitoring for 30 minutes after receiving the vaccine. Additional study visits will occur at Days 3, 5, 7, 10, 12, 14, 17, 19, 21, 28, and 56. These visits will include clinical assessments and nasal washes; on Day 56, a blood collection will also occur. On days where no study visit is scheduled (through Day 29), participants' parents or guardians will report participants' temperatures and signs of illness to researchers by e-mail or phone.
In October following vaccination, participants may have a pre-RSV season blood collection visit. During RSV season, November through March following vaccination, researchers will contact participants' parents or guardians on a weekly basis for follow-up monitoring. During this time frame, participants seen by a medical provider for fever, respiratory illness, or otitis media will have a study visit, which will include a nasal wash and clinical assessment. In April following vaccination, participants will undergo a final blood collection.
- Conditions
- Respiratory Syncytial Virus Infections
- Being tested
- RSV LID ΔM2-2 Vaccine, Placebo Vaccine
- Medical subject headings
- Respiratory Syncytial Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSV LID ΔM2-2 VaccineBiological
10^5.0 plaque forming units (PFU); 0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)
Placebo VaccineBiological
0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril)
| Study group | Role | What they receive |
|---|---|---|
| RSV LID ΔM2-2 Vaccine | Experimental | Participants will receive one dose of the RSV LID ΔM2-2 vaccine at study entry, delivered as nose drops. Receives: Biological: RSV LID ΔM2-2 Vaccine |
| Placebo Vaccine | Placebo comparator | Participants will receive one dose of placebo at study entry, delivered as nose drops. Receives: Biological: Placebo Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study, the first 28 days after inoculation
Measured: Measured through Day 28
Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study, the first 28 days after inoculation
Measured: Measured through Day 28
Frequency of vaccine-related lower respiratory illness
Measured: Measured through Day 56
Proportion of participants that develop 4-fold or greater rises in RSV-neutralizing antibody titer following vaccination
Antibody responses to the RSV F glycoprotein will also be assessed by enzyme-linked immunosorbent assay (ELISA).
Measured: Measured through Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Respiratory Syncytial Virus InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elizabeth McFarland, MD, Study chair, Children's Hospital Colorado
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02237209
- Sponsor's protocol ID
- IMPAACT 2000
- Other IDs
- DAIDS ES
- Status last verified
- Oct 2015
- First submitted
- 9 Sep 2014
- Last updated
- 8 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McFarland EJ, Karron RA, Muresan P, Cunningham CK, Valentine ME, Perlowski C, Thumar B, Gnanashanmugam D, Siberry GK, Schappell E, Barr E, Rexroad V, Yogev R, Spector SA, Aziz M, Patel N, Cielo M, Luongo C, Collins PL, Buchholz UJ; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2000 Study Team. Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children. J Infect Dis. 2018 Apr 11;217(9):1347-1355. doi: 10.1093/infdis/jiy040.
PubMed 29509911
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Safety and Immunogenicity of Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine RSV LID ΔM2-2 in RSV-Seronegative Infants and Children
- ClinicalTrials.gov ID
- NCT02237209
- Acronym / sponsor ID
- IMPAACT 2000
- Conditions
- Respiratory Syncytial Virus Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 11 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around the world. This study will evaluate the safety and immune response to an RSV vaccine in RSV-seronegative infants and children.
This study is a companion study to CIR 291.
Detailed description
RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in infants and children under 5 years of age in the world. RSV illness can range from mild upper respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia. Severe RSV disease in infancy may also predispose children to develop reactive airway disease during childhood. The purpose of this study is to evaluate the safety and immunogenicity of an RSV vaccine (RSV LID ΔM2-2) in RSV-seronegative infants and children at least 6 months and through 24 months of age.
To determine study eligibility, the screening process will include a blood collection. Screening may begin after the RSV season (i.e., as of April 1) and enrollment must precede the RSV season (no later than October 14). At study entry, eligible participants will be randomly assigned to receive one dose of either the RSV vaccine or placebo, which will be delivered as nose drops. Participants will also undergo a review of medical history, clinical assessment, and a nasal wash. They will then receive their assigned vaccine and will remain under observation for monitoring for 30 minutes after receiving the vaccine. Additional study visits will occur at Days 3, 5, 7, 10, 12, 14, 17, 19, 21, 28, and 56. These visits will include clinical assessments and nasal washes; on Day 56, a blood collection will also occur. On days where no study visit is scheduled (through Day 29), participants' parents or guardians will report participants' temperatures and signs of illness to researchers by e-mail or phone.
In October following vaccination, participants may have a pre-RSV season blood collection visit. During RSV season, November through March following vaccination, researchers will contact participants' parents or guardians on a weekly basis for follow-up monitoring. During this time frame, participants seen by a medical provider for fever, respiratory illness, or otitis media will have a study visit, which will include a nasal wash and clinical assessment. In April following vaccination, participants will undergo a final blood collection.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RSV LID ΔM2-2 Vaccine | Experimental | Biological: RSV LID ΔM2-2 VaccineParticipants will receive one dose of the RSV LID ΔM2-2 vaccine at study entry, delivered as nose drops. |
| Placebo Vaccine | Placebo comparator | Biological: Placebo VaccineParticipants will receive one dose of placebo at study entry, delivered as nose drops. |
Who may qualify
- Ages
- 6 to 24 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Participant is at least 6 months (defined as at least 180 days) of age at the time of screening and less than 25 months (defined as 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. Note: any questions regarding interpretation of this criterion should be forwarded to the team.
- Parents/guardians demonstrate their understanding of the study, sign the informed consent, and agree to administration of study product following a detailed explanation of the study
- Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening obtained no more than 42 days prior to scheduled inoculation
- Has a current height and weight above the 5th percentile for age
Key exclusion criteria (39 listed)
- Known or suspected HIV infection or impairment of immunological functions
- Receipt of immunosuppressive therapy, including any systemic corticosteroids within 30 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.
- 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) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSV LID ΔM2-2 Vaccine10^5.0 plaque forming units (PFU); 0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril) | Biological | RSV LID ΔM2-2 Vaccine |
| Placebo Vaccine0.5 mL dose delivered as nose drops (approximately 0.25 mL per nostril) | Biological | Placebo Vaccine |
Primary outcome
Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study, the first 28 days after inoculation
Time frame: Measured through Day 28
Severity of vaccine-related solicited AEs that occur during the acute monitoring phase of the study, the first 28 days after inoculation
Time frame: Measured through Day 28
Frequency of vaccine-related lower respiratory illness
Time frame: Measured through Day 56
Proportion of participants that develop 4-fold or greater rises in RSV-neutralizing antibody titer following vaccination
Time frame: Measured through Day 56
Antibody responses to the RSV F glycoprotein will also be assessed by enzyme-linked immunosorbent assay (ELISA).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2015.
- Derived from this study: PubMed 29509911McFarland EJ, Karron RA, Muresan P, Cunningham CK, Valentine ME, Perlowski C, Thumar B, Gnanashanmugam D, Siberry GK, Schappell E, Barr E, Rexroad V, Yogev R, Spector SA, Aziz M, Patel N, Cielo M, Luongo C, Collins PL, Buchholz UJ; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 2000 Study Team. Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children. J Infect Dis. 2018 Apr 11;217(9):1347-1355. doi: 10.1093/infdis/jiy040.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth McFarland, MD study chair
Children's Hospital Colorado
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RSV LID ΔM2-2 Vaccine in people with Respiratory Syncytial Virus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of vaccine-related solicited adverse events (AEs) that occur during the acute monitoring phase of the study, the first 28 days after inoculation (time frame: Measured through Day 28). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02237209, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2015.