- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT02890381
Evaluating the Infectivity, Safety and Immunogenicity of a Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine (RSV LID cp ΔM2-2) in RSV-Seronegative Infants 6 to 24 Months of Age (LID)
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 6 to 24 Months of Age
The purpose of this study was to evaluate the safety, infectivity, and immunogenicity of a single intranasal dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants 6 to 24 months of age.
This study was a companion study to CIR 312.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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 LID cp ΔM2-2, a recombinant live-attenuated RSV vaccine, in RSV-seronegative infants 6 to 24 months of age.
Participants were randomly assigned to receive a single dose of the RSV LID cp ΔM2-2 vaccine or placebo at study entry (Day 0).
Participants were enrolled in the study between April 1 and October 14 (outside of RSV season) and 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 10 months, depending on when they enrolled in the study. Participants attended several study visits throughout the study, which may include 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.
The study was closed to accrual early after interim data were reviewed by a subset of protocol team members and it was concluded that this vaccine candidate will not meet the criteria listed in the protocol for a good vaccine candidate. This recommendation was shared with the (blinded) protocol chair and the Medical Officers, as well as the Data Safety and Monitoring Board (DSMB), who agreed with the unblinded protocol team members' assessment. The targeted sample size was 33 (22 in the vaccine arm and 11 in the placebo arm). Participants already on study at the time of the early closing decision remained on study and completed the follow-up per protocol.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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California
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Los Angeles, California, États-Unis, 90095-1752
- David Geffen School of Medicine at UCLA NICHD CRS
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Colorado
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Aurora, Colorado, États-Unis, 80045
- Univ. of Colorado Denver NICHD CRS
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Illinois
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Chicago, Illinois, États-Unis, 60612
- Rush Univ. Cook County Hosp. Chicago NICHD CRS
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Maryland
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Baltimore, Maryland, États-Unis, 21205
- Johns Hopkins University Center for Immunization Research
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis, 19104
- Philadelphia IMPAACT Unit CRS
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Greater than or equal to 6 months (defined as greater than or equal to 180 days) of age at the time of screening and less than 25 months (defined as less than 750 days) of age.
- Good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.
- Parents/guardians willing and able to provide written informed consent as described in the protocol.
- Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening from a sample collected no more than 42 days prior to inoculation. Note: results from specimens collected during screening for IMPAACT 2011 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.
- Received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices [ACIP]).
- Expected to be available for the duration of the study.
- If born to an HIV-infected woman, participant must not have been breastfed and must have had documentation of 2 negative HIV nucleic acid (RNA or DNA) test results from samples collected on different dates with both collected when greater than or equal to 1 month of age and at least one collected when greater than or equal to 4 months of age, and no positive HIV nucleic acid (RNA or DNA) test; or 2 negative HIV antibody tests, both from samples collected at greater than or equal to 6 months of age.
Exclusion Criteria:
- 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 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.
- 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 were allowed to enroll.
- 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 enrolled, or scheduled to be enrolled in IMPAACT 2011, 2012 or 2013 AND 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 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 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 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 has 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 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 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur placebo: Placebo
Les participants ont reçu une dose unique de placebo à l'entrée dans l'étude (jour 0).
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Diluant isotonique, administré sous forme de gouttes nasales
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Expérimental: RSV LID cp ΔM2-2 Vaccine
Participants received a single dose of the RSV LID cp ΔM2-2 vaccine at study entry (Day 0).
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10 ^ 5 unités formant plaque (PFU); administré sous forme de gouttes nasales
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Titre maximal de rejet du virus vaccinal
Délai: Mesuré aux jours 0, 3, 5, 7, 10, 12, 14, 17 et 28
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Il s'agit de la valeur la plus élevée par participant du titre de virus vaccinal excrété.
Il a été mesuré par la culture.
Seuls les participants répondant à la définition d'infection par le virus du vaccin ont été inclus.
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Mesuré aux jours 0, 3, 5, 7, 10, 12, 14, 17 et 28
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Durée de l'excrétion du virus dans les lavages nasaux
Délai: Mesuré aux jours 0, 3, 5, 7, 10, 12, 14, 17 et 28. Le dernier jour positif est signalé.
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Déterminé séparément par a) culture et b) réaction en chaîne par polymérase de transcription inverse (RT-PCR)
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Mesuré aux jours 0, 3, 5, 7, 10, 12, 14, 17 et 28. Le dernier jour positif est signalé.
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Nombre de participants avec EI non sollicités par niveau
Délai: Mesuré du jour 0 au jour 28
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Les événements indésirables non sollicités étaient d'autres événements, non inclus dans les EI sollicités.
Le nombre de participants ayant subi des événements indésirables sollicités a été présenté.
Un participant n'a été compté qu'une seule fois dans chaque catégorie d'EI non sollicité, et c'est dans la ligne correspondant à l'événement indésirable de grade le plus élevé qu'il a eu dans cette catégorie.
Le classement des AE (Grade 1 - léger à 4 - mettant la vie en danger) a été effectué par le tableau de classement DAIDS AE v2.0 (voir les références).
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Mesuré du jour 0 au jour 28
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Nombre de participants infectés par le vaccin contre le VRS
Délai: Mesuré aux jours 0, 3, 5, 7, 10, 12, 14, 17 et 28 pour les lavages nasaux, et aux jours 0, 56 pour les anticorps sériques neutralisant le VRS
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Défini comme 1) virus vaccinal identifié dans un lavage nasal du jour d'étude 0 à 28 (un résultat binaire basé sur les lavages nasaux) ou 2) supérieur ou égal à une augmentation de 4 fois du titre d'anticorps neutralisant le VRS sérique entre les jours d'étude 0 et 56.
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Mesuré aux jours 0, 3, 5, 7, 10, 12, 14, 17 et 28 pour les lavages nasaux, et aux jours 0, 56 pour les anticorps sériques neutralisant le VRS
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Réponses d'anticorps sériques à la glycoprotéine F du VRS évaluées par dosage immuno-enzymatique (ELISA)
Délai: Mesuré au jour 56
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L'immunogénicité a été évaluée environ 2 mois après l'inoculation (jour d'étude 56).
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Mesuré au jour 56
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Number of Participants With Solicited Adverse Events (AEs) by Grade
Délai: Measured from Day 0 through Day 28
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Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI).
The number of participants who experienced solicited adverse events was presented.
A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category.
These events were graded (Grade 1-mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 3 and Table 4 in the protocol document.
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Measured from Day 0 through Day 28
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Number of Participants With Serious Adverse Events (SAEs)
Délai: Measured from Day 0 through Day 56
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A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that:
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Measured from Day 0 through Day 56
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Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titer
Délai: Measured at Day 0 and Day 56
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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 and post time points.
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Measured at Day 0 and Day 56
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Participants Who Had Symptomatic, Medically Attended Respiratory and Febrile Illness, by Grade, Among Those Who Experienced Natural Infection With wt RSV During the Subsequent RSV Season
Délai: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
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The number of participants who had symptomatic, medically attended respiratory and febrile illness among those who had RSV detected in nasal washes or >=4 fold rise in serum antibodies during the subsequent RSV season were 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.
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Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
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Magnitude of Serum RSV-neutralizing Antibody Responses in the Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the Subsequent RSV Season.
Délai: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
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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.
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Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
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Number of Participants With B Cell Responses to Vaccine
Délai: Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
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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, and between pre- and post-RSV surveillance time points.
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Measured through participant's last study visit, up to a total of 6 to 10 months depending on when participants enroll in the study
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Collaborateurs et enquêteurs
Les enquêteurs
- Chaise d'étude: Coleen Cunningham, MD, Children's Health Center, DUMC
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- IMPAACT 2012
- 30073 (Identificateur de registre: DAIDS-ES Registry Number)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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