A Phase 1b/2a Randomized, Double-Blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm Infants (MEDI8897 1b)
18 septembre 2018 mis à jour par: MedImmune LLC
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of an extended half-life anti-respiratory syncytial virus (RSV) monoclonal antibody compared to placebo when administered to healthy preterm infants.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This Phase 1b/2a study will be a dose-escalation design to begin data collection on PK and safety in children.
The population to be enrolled is healthy preterm infants born between 32 weeks 0 days and 34 weeks 6 days gestation who would not receive RSV prophylaxis based on the American Academy of Pediatrics (AAP) or other local guidelines.
These subjects will not be receiving palivizumab, allowing for a placebo comparator group to begin collecting data on incidence rates of RSV medically attended lower respiratory illness (MA-LRI) and efficacy.
Enrollment is planned at approximately 20 sites in the USA, Chile, and South Africa.
Type d'étude
Interventionnel
Inscription (Réel)
151
Phase
- La phase 1
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Cape Town, Afrique du Sud
- Research Site
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East London, Afrique du Sud
- Research Site
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Johannesburg, Afrique du Sud
- Research Site
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Pretoria, Afrique du Sud
- Research Site
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Santiago, Chili
- Research Site
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Valdivia, Chili
- Research Site
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California
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Anaheim, California, États-Unis
- Research Site
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Ontario, California, États-Unis
- Research Site
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New York
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Syracuse, New York, États-Unis
- Research Site
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Ohio
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Cleveland, Ohio, États-Unis
- Research Site
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South Carolina
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Charleston, South Carolina, États-Unis
- Research Site
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Utah
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Saint George, Utah, États-Unis
- Research Site
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Wisconsin
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Marshfield, Wisconsin, États-Unis
- Research Site
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
Pas plus vieux que 1 an (Enfant)
Accepte les volontaires sains
Oui
Sexes éligibles pour l'étude
Tout
La description
Key Inclusion Criteria:
- Healthy infants born between 32 weeks 0 days and 34 weeks 6 days gestational age
- Infants who are entering their first RSV season at the time of screening
Key Exclusion Criteria:
- Gestational age < 32 weeks 0 days and >34 weeks 6 days
- Meets AAP or other local criteria to receive commercial palivizumab
- Any fever (≥ 100.4°F [≥ 38.0°C], regardless of route) or lower respiratory illness within 7 days prior to randomization
- Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization
- Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection
- Receipt of palivizumab or any RSV vaccine, including maternal RSV vaccination
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
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
Participants will receive placebo intramuscularly.
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Participants will receive placebo intramuscularly.
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Expérimental: MEDI8897 10 mg
Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
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Participants will receive a single dose of MEDI8897 10 milligram (mg) intramuscularly.
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Expérimental: MEDI8897 25 mg
Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
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Participants will receive a single dose of MEDI8897 25 mg intramuscularly.
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Expérimental: MEDI8897 50 mg
Participants will receive a single dose of MEDI8897 50 mg intramuscularly.
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Participants will receive a single dose of MEDI8897 50 mg intramuscularly.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Délai: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
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An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity of a participant who received MEDI8897.
TEAEs and TESAEs were the events that occurred between administration of study drug (Day 1) and Day 361 that were absent before treatment or that worsened relative to pre-treatment state.
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From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
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Number of Participants With Treatment-Emergent Adverse Events of Special Interest
Délai: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
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An AESI was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator (that is, within 24 hrs of knowledge of the event) to the sponsor.
The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, hypersensitivity reactions including anaphylaxis, immune complex disease, and thrombocytopenia.
Treatment-emergent AESIs were collected from the time of dosing until Day 361 post-dose.
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From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
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Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events
Délai: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)
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Laboratory abnormalities determined by the investigator to be clinically significant that occurred after study drug dosing through 151 days post-dose that were absent before treatment or that worsened relative to pre-treatment state were reported as TEAEs.
Laboratory evaluations (haematology and serum chemistry) of blood samples were performed.
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From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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The Tmax defined as time at which maximum observed concentration of MEDI8897 (Cmax) was observed.
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Maximum Observed Serum Concentration (Cmax) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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The Cmax is the maximum observed serum concentration of MEDI8897.
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), and 150 (± 7) Post-dose
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Area under the concentration-time curve of the MEDI8897 in serum over the time interval from day 1 to day 151 (AUC1-151).
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), and 150 (± 7) Post-dose
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Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of MEDI8897.
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Terminal Elimination Half Life (t1/2) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Extravascular Clearance (CL/F) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Extravascular Volume of Distribution (Vz/F) of MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
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Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose
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Number of Participants Positive for Anti-Drug Antibodies to MEDI8897
Délai: Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose
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A participant was considered ADA-positive if the participant had a positive reading at any time point post baseline.
Titers greater than or equal to 50 were considered positive.
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Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
13 janvier 2015
Achèvement primaire (Réel)
28 septembre 2016
Achèvement de l'étude (Réel)
28 septembre 2016
Dates d'inscription aux études
Première soumission
17 octobre 2014
Première soumission répondant aux critères de contrôle qualité
10 novembre 2014
Première publication (Estimation)
14 novembre 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
19 septembre 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
18 septembre 2018
Dernière vérification
1 septembre 2018
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- D5290C00002
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