Respiratory Syncytial Virus InfectionsPhase 1NCT03102034
Evaluating the Infectivity, Safety, and Immunogenicity of a Single Dose of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (D46/NS2/N/ΔM2-2-HindIII) in RSV-Seronegative Infants 6 to 24 Months of Age
A Phase 1 study testing D46/NS2/N/ΔM2-2-HindIII in people with Respiratory Syncytial Virus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
Trial 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 and children 6 to 24 months of age. This study was a companion study to CIR 313. 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?
- D46/NS2/N/ΔM2-2-HindIII
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 10 sitesUnited States
- Study dates
- 6 Apr 2017to 25 May 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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. Note: results from specimens collected during screening for any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (NIAID, NIH) were acceptable as long as within the 42-day window.
- 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.
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- 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 was indicated only if the participant was age-eligible per 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 4 weeks of age and at least one collected when greater than or equal to 16 weeks 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 24 weeks of age.
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 was 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 in any IMPAACT RSV study) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV immunoglobulin [IG] or RSV monoclonal antibody [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 diagnosed wheezing.
- Member of a household that contained, or would contain, an infant who was less than 6 months of age at the enrollment date through Day 28.
- Member of a household that contains another child who was, or was scheduled to be, enrolled in IMPAACT 2011, 2012 or 2013 or another study evaluating an intranasal live-attenuated RSV vaccine, 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 contained 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
- a person who had received chemotherapy within the 12 months prior to enrollment; or
- a person receiving immunosuppressant agents; or
- a person living with a solid organ or bone marrow transplant.
- Verbal report of CD4 T cell lymphocyte was sufficient documentation if the parent/guardian was confident of history.
- Attended a daycare facility and shared a room with infants less than 6 months of age, and parent/guardian was 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 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
- 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
- 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.
- Suspected or documented developmental disorder, delay, or other developmental problem.
- Previous receipt of supplemental oxygen therapy in a home setting.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University School of Medicine NICHD CRS
Atlanta, Georgia, 30322
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
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
Usc La Nichd Crs
Los Angeles, California, 90089
David Geffen School of Medicine at UCLA NICHD CRS
Los Angeles, California, 90095-1752
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
SUNY Stony Brook NICHD CRS
Stony Brook, New York, 11794
Jacobi Med. Ctr. Bronx NICHD CRS
The Bronx, New York, 10461
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, D46/NS2/N/ΔM2-2-HindIII, Lot RSV#011B, Delivered as Nose Drops to RSV-Seronegative Infants 6 to 24 Months of Age
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 and children 6 to 24 months of age.
This study was a companion study to CIR 313.
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 evaluated the safety, infectivity, and immunogenicity of a single dose of RSV D46/NS2/N/ΔM2-2-HindIII, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.
Participants were randomly assigned to receive a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine or placebo (administered as nose drops) at study entry (Day 0).
Participants could be enrolled in the study outside of RSV season (between April 1 and October 14 for most sites or-for sites with local RSV seasons that start earlier-as specified on a site-by-site basis in the Manual Of Procedures). All participants remained on study until they completed the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration was between 6 and 13 months, depending on when they enrolled in the study. Participants attended several study visits throughout the study, which included physical examinations, blood collection, and nasal washes. Participants' parents or guardians were contacted by study staff at various times during the study to monitor participants' health.
- Conditions
- Respiratory Syncytial Virus Infections
- Being tested
- D46/NS2/N/ΔM2-2-HindIII, 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.
D46/NS2/N/ΔM2-2-HindIIIBiological
10^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops
PlaceboBiological
Isotonic diluent; administered as nose drops
| Study group | Role | What they receive |
|---|---|---|
| RSV D46/NS2/N/ΔM2-2-HindIII Vaccine | Experimental | Participants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0). Receives: Biological: D46/NS2/N/ΔM2-2-HindIII |
| Placebo | Placebo comparator | Participants received 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.
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 was 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 3 and Table 4 in the protocol document.
Measured: 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 was 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: Measured from Day 0 through Day 28
Number of Participants With Serious Adverse Events (SAEs)
A Serious Adverse Event (SAE) was an AE, whether considered related to the study product or not, that:
- Resulted in death during the period of protocol-defined surveillance
- Was life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death were it more severe
- Required 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
- Resulted in a persistent or significant disability/incapacity
- Was a congenital anomaly or birth defect
- Was an important medical event that might not be immediately life threatening or result in death or hospitalization but might jeopardize the patient or might require intervention to prevent one of the outcomes listed above.
Measured: Measured from Day 0 through Day 56
Number of Participants Infected With RSV Vaccine Virus
Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) and/or 2) greater than or equal to 4-fold rise in RSV-neutralizing antibody titer from Study Day 0 and 56.
Measured: 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: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28
Duration of Vaccine Virus Shedding in Nasal Washes
Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Measured: 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: 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: Measured at Day 56
Secondary outcomes (3)
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season
The number of participants who had RSV-associated, medically attended, acute respiratory illness (RSV-MAARI) or RSV-associated, medically attended, acute lower respiratory illness (RSV-MAALRI) among those who had RSV detected in nasal washes or greater than or equal to 4 fold rise in serum antibodies during the subsequent RSV season were presented.
Measured: Measured from November 1st through participant's post-RSV season surveillance visit
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.
Only participants who had RSV detected in nasal washes or a greater than or equal to 4-fold rise in serum antibodies during the subsequent RSV season were included. RSV-neutralizing antibody titers were measured pre- and post-RSV surveillance season.
Measured: Measured through participant's last study visit, up to a total of 6 to 13 months depending on when participants enrolled in the study
Number of Participants With B Cell Responses to Vaccine
A B cell response to vaccine is indicated by a greater than or equal to 4-fold change in serum antibody titers to RSV F glycoprotein between the pre- and post-inoculation time points.
Measured: Measured at day 0 and Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2017
- Study start6 Apr 2017
- Primary completion25 May 2018
- Study completion25 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- 32 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Elizabeth (Betsy) J. McFarland, MD, Study chair, University of Colorado School of Medicine and Children's Hospital Colorado, Pediatric Infectious Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03102034
- Sponsor's protocol ID
- IMPAACT 2013
- Other IDs
- 30074
- Status last verified
- Jan 2022
- First submitted
- 23 Mar 2017
- Last updated
- 8 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
McFarland EJ, Karron RA, Muresan P, Cunningham CK, Perlowski C, Libous J, Oliva J, Jean-Philippe P, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Cielo M, Wiznia A, Deville JG, Yang L, Luongo C, Collins PL, Buchholz UJ. Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children. J Infect Dis. 2020 Jun 11;221(12):2050-2059. doi: 10.1093/infdis/jiaa049.
PubMed 32006006
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2022. 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, D46/NS2/N/ΔM2-2-HindIII, Lot RSV#011B, Delivered as Nose Drops to RSV-Seronegative Infants 6 to 24 Months of Age
- ClinicalTrials.gov ID
- NCT03102034
- Acronym / sponsor ID
- IMPAACT 2013
- Conditions
- Respiratory Syncytial Virus Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 6 Apr 2017 (actual)
- Primary completion
- 25 May 2018 (actual)
- Study completion
- 25 May 2018 (actual)
- First posted
- 5 Apr 2017 (actual)
- Results
- Posted 14 Jun 2019
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 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 and children 6 to 24 months of age.
This study was a companion study to CIR 313.
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 evaluated the safety, infectivity, and immunogenicity of a single dose of RSV D46/NS2/N/ΔM2-2-HindIII, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants and children 6 to 24 months of age.
Participants were randomly assigned to receive a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine or placebo (administered as nose drops) at study entry (Day 0).
Participants could be enrolled in the study outside of RSV season (between April 1 and October 14 for most sites or-for sites with local RSV seasons that start earlier-as specified on a site-by-site basis in the Manual Of Procedures). All participants remained on study until they completed the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. Participants' total study duration was between 6 and 13 months, depending on when they enrolled in the study. Participants attended several study visits throughout the study, which included physical examinations, blood collection, and nasal washes. Participants' parents or guardians were 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 D46/NS2/N/ΔM2-2-HindIII Vaccine | Experimental | Biological: D46/NS2/N/ΔM2-2-HindIIIParticipants received a single dose of the D46/NS2/N/ΔM2-2-HindIII vaccine at study entry (Day 0). |
| Placebo | Placebo comparator | Biological: PlaceboParticipants received 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)
- 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. Note: results from specimens collected during screening for any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (NIAID, NIH) were acceptable as long as within the 42-day window.
- Growing at a normal velocity for age (as demonstrated on a standard growth chart) AND
- 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 was indicated only if the participant was age-eligible per ACIP.
Key exclusion criteria (45 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 was 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 in any IMPAACT RSV study) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV immunoglobulin [IG] or RSV monoclonal antibody [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 |
|---|---|---|
| D46/NS2/N/ΔM2-2-HindIII10^5 plaque-forming units (PFU) per 0.5ml vaccine; administered as nose drops | Biological | RSV D46/NS2/N/ΔM2-2-HindIII Vaccine |
| PlaceboIsotonic diluent; administered as nose drops | Biological | Placebo |
Primary outcome
Number of Participants With Solicited Adverse Events (AEs) by Grade
Time frame: Measured from Day 0 through Day 28
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 was 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 3 and Table 4 in the protocol document.
Number of Participants With Unsolicited AEs by Grade
Time frame: Measured from Day 0 through Day 28
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 was 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).
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Measured from Day 0 through Day 56
A Serious Adverse Event (SAE) was an AE, whether considered related to the study product or not, that: * Resulted in death during the period of protocol-defined surveillance * Was life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it did not refer to an event that hypothetically might have caused death were it more severe * Required 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 * Resulted in a persistent or significant disability/incapacity * Was a congenital anomaly or birth defect * Was an important medical event that might not be immediately life threatening or result in death or hospitalization but might jeopardize the patient or might require intervention to prevent one of the outcomes listed above.
Number of Participants Infected With RSV Vaccine Virus
Time frame: 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
Defined as 1) vaccine virus identified in a nasal wash from Study Day 0-28 (a binary outcome based on nasal washes) and/or 2) greater than or equal to 4-fold rise in RSV-neutralizing antibody titer from Study Day 0 and 56.
Peak Titer of Vaccine Virus Shed
Time frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28
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.
Duration of Vaccine Virus Shedding in Nasal Washes
Time frame: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17, and 28. Last day positive is reported.
Determined separately by a) culture and b) reverse transcription polymerase chain reaction (RT-PCR)
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer
Time frame: Measured at Day 0 and Day 56
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.
Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)
Time frame: Measured at Day 56
Immunogenicity was assessed at approximately 2 months post-inoculation (Study Day 56).
3 secondary outcomes
Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season
Time frame: Measured from November 1st through participant's post-RSV season surveillance visit
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.
Time frame: Measured through participant's last study visit, up to a total of 6 to 13 months depending on when participants enrolled in the study
Number of Participants With B Cell Responses to Vaccine
Time frame: Measured at day 0 and Day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32006006McFarland EJ, Karron RA, Muresan P, Cunningham CK, Perlowski C, Libous J, Oliva J, Jean-Philippe P, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Cielo M, Wiznia A, Deville JG, Yang L, Luongo C, Collins PL, Buchholz UJ. Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children. J Infect Dis. 2020 Jun 11;221(12):2050-2059. doi: 10.1093/infdis/jiaa049.
- DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014Link provided by the sponsor.
- Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010Link provided by the sponsor.
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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 (Betsy) J. McFarland, MD study chair
University of Colorado School of Medicine and Children's Hospital Colorado, Pediatric Infectious Diseases
10 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 D46/NS2/N/ΔM2-2-HindIII in people with Respiratory Syncytial Virus Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 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 45 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 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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?
Yes. Results are posted in the registry (first posted 14 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Solicited Adverse Events (AEs) by Grade (time frame: Measured from Day 0 through Day 28). The study lists 8 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 NCT03102034, 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 Feb 2022.