Respiratory Syncytial Virus InfectionsPhase 1NCT02948127
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
A Phase 1 study testing RSV LID cp ΔM2-2 Vaccine in people with Respiratory Syncytial Virus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial 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. 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 cp ΔM2-2 Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2016to 30 Apr 2018
- 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
- 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
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- 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
Who cannot join
- 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.
- 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
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- 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
- 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°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 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 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
- Receipt of any of the following medications within 3 days of 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
- Receipt of salicylate (aspirin) or salicylate-containing products within the past 28 days
- 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
- Suspected or documented developmental disorder, delay, or other developmental problem
- Previous receipt of supplemental oxygen therapy in a home setting
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, 21205
Center for Immunization Research East, Johns Hopkins Bayview Medical Center Campus
Baltimore, Maryland, 21224
Center for Immunization Research South
Laurel, Maryland, 20708
About this study
Official title: Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, LID cp ΔM2-2, Lot RSV#009B, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
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.
Read the detailed 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 safety, infectivity, and immunogenicity of a single dose of RSV LID cp ΔM2-2, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.
Participants will be randomly assigned to receive a single dose of the RSV LID cp ΔM2-2 vaccine or placebo at study entry (Day 0).
Participants will be enrolled in the study between April 1 and October 31 (outside of RSV season) and 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 will be between 6 and 13 months, depending on when they enroll in the study. Participants will be evaluated in study visits that may include physical examinations, blood collection, and nasal washes. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.
- Conditions
- Respiratory Syncytial Virus Infections
- Being tested
- RSV LID cp ΔM2-2 Vaccine, Placebo
- 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 cp ΔM2-2 VaccineBiological
10^5 plaque-forming units (PFUs); administered as nose drops
PlaceboBiological
Administered as nose drops
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Biological: RSV LID cp ΔM2-2 Vaccine |
| Placebo | Placebo comparator | Participants will receive a single dose of placebo at study entry (Day 0). Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grades of study product-related solicited adverse events (AEs)
Measured: Measured through Day 28
Grades of study product-related unsolicited AEs
Measured: Measured through Day 28
Grades of study product-related serious adverse events (SAEs)
Measured: 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: Measured through Day 56
Peak titer of vaccine virus shed
Measured: Measured through Day 28
Duration of vaccine virus shedding in nasal washes measured by culture
Measured: Measured through Day 28
Duration of vaccine virus shedding in nasal washes measured by RT-PCR
Measured: Measured through Day 28
Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer
Measured: Measured through Day 56
Antibody responses to RSV F glycoprotein as assessed by enzyme-linked immunosorbent assay (ELISA)
Measured: 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
Will be measured through the subsequent RSV season (November 1 in the calendar year of study entry to March 31 in the calendar year following study entry)
Measured: 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
Will be measured at the post-RSV season visit (between April 1 and April 30 in the calendar year following study entry)
Measured: 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
Will be measured at the post-RSV season visit (between April 1 and April 30 in the calendar year following study entry)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study startSep 2016
- Primary completion30 Apr 2017
- Study completion30 Apr 2018
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
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ruth Karron, MD, Principal investigator, Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02948127
- Sponsor's protocol ID
- CIR 312
- Status last verified
- Aug 2018
- First submitted
- 25 Oct 2016
- Last updated
- 17 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31211158
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, LID cp ΔM2-2, Lot RSV#009B, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
- ClinicalTrials.gov ID
- NCT02948127
- Acronym / sponsor ID
- CIR 312
- Conditions
- Respiratory Syncytial Virus Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 2016
- Primary completion
- 30 Apr 2017 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 28 Oct 2016 (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.
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.
Detailed 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 safety, infectivity, and immunogenicity of a single dose of RSV LID cp ΔM2-2, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.
Participants will be randomly assigned to receive a single dose of the RSV LID cp ΔM2-2 vaccine or placebo at study entry (Day 0).
Participants will be enrolled in the study between April 1 and October 31 (outside of RSV season) and 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 will be between 6 and 13 months, depending on when they enroll in the study. Participants will be evaluated in study visits that may include physical examinations, blood collection, and nasal washes. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.
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 cp ΔM2-2 Vaccine | Experimental | Biological: RSV LID cp ΔM2-2 VaccineParticipants will receive a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0). |
| Placebo | Placebo comparator | Biological: PlaceboParticipants will receive a single dose of placebo at study entry (Day 0). |
Who may qualify
- Ages
- 6 to 24 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (41 listed)
- 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.
- 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)
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 cp ΔM2-2 Vaccine10^5 plaque-forming units (PFUs); administered as nose drops | Biological | RSV LID cp ΔM2-2 Vaccine |
| PlaceboAdministered as nose drops | Biological | Placebo |
Primary outcome
Grades of study product-related solicited adverse events (AEs)
Time frame: Measured through Day 28
Grades of study product-related unsolicited AEs
Time frame: Measured through Day 28
Grades of study product-related serious adverse events (SAEs)
Time frame: Measured through Day 56
Number of participants with infection with vaccine virus
Time frame: Measured through Day 56
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
Peak titer of vaccine virus shed
Time frame: Measured through Day 28
Duration of vaccine virus shedding in nasal washes measured by culture
Time frame: Measured through Day 28
Duration of vaccine virus shedding in nasal washes measured by RT-PCR
Time frame: Measured through Day 28
Frequency of a greater than or equal to 4-fold rise in RSV-neutralizing antibody titer
Time frame: Measured through Day 56
Antibody responses to RSV F glycoprotein as assessed by enzyme-linked immunosorbent assay (ELISA)
Time frame: Measured through Day 56
3 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
- Derived from this study: PubMed 31211158Cunningham 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.
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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.
Ruth Karron, MD principal investigator
Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health (JHSPH)
3 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 cp ΔM2-2 Vaccine in people with Respiratory Syncytial Virus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 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 9 inclusion and 41 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: stopped early, as of the sponsor's last update on 17 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 was stopped early. Results are not available in the source record.
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?
Grades of study product-related solicited adverse events (AEs) (time frame: Measured through Day 28). The study lists 9 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 NCT02948127, 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 17 Aug 2018.