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NCT03102034

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

Completed Phase 1 Results posted Last updated 8 February 2022
What this trial tests

Phase 1 trial testing D46/NS2/N/ΔM2-2-HindIII in Respiratory Syncytial Virus Infections in 32 participants. Completed in 25 May 2018.

Timeline
6 April 2017
Primary endpoint
25 May 2018
25 May 2018

Quick facts

Lead sponsorNational Institute of Allergy and Infectious Diseases (NIAID)
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposeprevention
Enrollment32
Start date6 April 2017
Primary completion25 May 2018
Estimated completion25 May 2018
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 6 Months to 24 Months, any sex, with Respiratory Syncytial Virus Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Solicited Adverse Events (AEs) by Grade Primary · 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.

Fever
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine17
Placebo9
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine3
Placebo1
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo1
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Otitis Media
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine21
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Upper Respiratory Illness (URI)
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine6
Placebo10
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine15
Placebo1
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Lower Respiratory Illness (LRI)
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine21
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Cough, without LRI
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine9
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine12
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Number of Participants With Unsolicited AEs by Grade Primary · 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).

Diarrhea, vomiting
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine17
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine4
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Epistaxis
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo10
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo1
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Nasal congestion
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Sneezing
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Eczema, Diaper rash
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine19
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine2
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Middle ear effusion
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Irritability
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Lymphadenopathy
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo11
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Number of Participants With Serious Adverse Events (SAEs) Primary · 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 ad

GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo0
Number of Participants Infected With RSV Vaccine Virus Primary · 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.

GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine21
Placebo0
Peak Titer of Vaccine Virus Shed Primary · 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.

GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine3.52.9 – 3.8
Duration of Vaccine Virus Shedding in Nasal Washes Primary · 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)

Culture positive
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine107 – 12
RT-PCR positive
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine1412 – 17
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer Primary · 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.

GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine20
Placebo0
Serum Antibody Responses to RSV F Glycoprotein as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) Primary · Measured at Day 56

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

GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine15.713.9 – 15.7
Placebo8.16 – 9.1
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 Secondary · Measured from November 1st through participant's post-RSV season surveillance visit

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.

RSV-MAARI
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine2
Placebo3
RSV-MAALRI
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine0
Placebo1
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. Secondary · Measured through participant's last study visit, up to a total of 6 to 13 months depending on when participants enrolled in the study

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.

Pre-RSV surveillance
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine6.34.5 – 7.7
Placebo2.32.3 – 2.8
Post-RSV Surveillance
GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine10.46.4 – 11.0
Placebo7.15.9 – 8.8
Number of Participants With B Cell Responses to Vaccine Secondary · Measured at day 0 and Day 56

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.

GroupValue95% CI
RSV D46/NS2/N/ΔM2-2-HindIII Vaccine21
Placebo0

Adverse events — posted to ClinicalTrials.gov

Time frame: From study entry to end of study. The duration of follow-up for a given participant was between 6 and 13 months depending on time of enrollment.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vaccine
Serious: 0/21 (0%)
Deaths: 0/21
Placebo
Serious: 0/11 (0%)
Deaths: 0/11
Other adverse events (15 terms — click to expand)

ReactionSystemVaccinePlacebo
RhinorrhoeaRespiratory, thoracic and mediastinal disorders——
CoughRespiratory, thoracic and mediastinal disorders——
PyrexiaGeneral disorders——
DiarrhoeaGastrointestinal disorders——
Otitis media acuteInfections and infestations——
Upper respiratory tract infectionInfections and infestations——
Decreased appetiteMetabolism and nutrition disorders——
Nasal congestionRespiratory, thoracic and mediastinal disorders——
Infantile vomitingGastrointestinal disorders——
LymphadenopathyBlood and lymphatic system disorders——
Conjunctivitis viralInfections and infestations——
Respiratory syncytial virus bronchiolitisInfections and infestations——
EpistaxisRespiratory, thoracic and mediastinal disorders——
WheezingRespiratory, thoracic and mediastinal disorders——
RashSkin and subcutaneous tissue disorders——

Data from ClinicalTrials.gov NCT03102034 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Past, Present and Future Approaches to the Prevention and Treatment of Respiratory Syncytial Virus Infection in Children.
    Simões EAF, Bont L, Manzoni P, Fauroux B, et al · · 2018 · cited 116× · PMID 29470837 · DOI 10.1007/s40121-018-0188-z
  2. Respiratory syncytial virus: from pathogenesis to potential therapeutic strategies.
    Shang Z, Tan S, Ma D. · · 2021 · cited 74× · PMID 34671221 · DOI 10.7150/ijbs.64762
  3. Live-attenuated Vaccines Prevent Respiratory Syncytial Virus-associated Illness in Young Children.
    Karron RA, Atwell JE, McFarland EJ, Cunningham CK, et al · · 2021 · cited 55× · PMID 32871092 · DOI 10.1164/rccm.202005-1660oc
  4. The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review.
    Shan J, Britton PN, King CL, Booy R. · · 2021 · cited 47× · PMID 33764693 · DOI 10.1111/irv.12850
  5. Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children.
    McFarland EJ, Karron RA, Muresan P, Cunningham CK, et al · · 2020 · cited 41× · PMID 32006006 · DOI 10.1093/infdis/jiaa049
  6. Development of Nasal Vaccines and the Associated Challenges.
    Nian X, Zhang J, Zhang J, Huang S, et al · · 2022 · cited 33× · PMID 36297419 · DOI 10.3390/pharmaceutics14101983
  7. Innate Immune Components that Regulate the Pathogenesis and Resolution of hRSV and hMPV Infections.
    Andrade CA, Pacheco GA, Gálvez NMS, Soto JA, et al · · 2020 · cited 24× · PMID 32545470 · DOI 10.3390/v12060637
  8. Nanoplatform Based Intranasal Vaccines: Current Progress and Clinical Challenges.
    Bai Z, Wan D, Lan T, Hong W, et al · · 2024 · cited 14× · PMID 39185745 · DOI 10.1021/acsnano.3c10797

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