Longitudinal Analysis And Sample Collection To Evaluate PML Risk Host Markers for PML Risk Host Markers for PML Risk (SRA-001)
17 février 2021 mis à jour par: John F. Foley, MD, Rocky Mountain MS Research Group, LLC
Longitudinal Meta-Analysis and Further Sample Collection To Evaluate Potential Host Markers for PML Risk
The purpose of the study is to develop an improved understanding of the long term pharmacokinetics and pharmacodynamics of natalizumab with both standard dosing and extended dosing, and collect additional samples to explore cell-based biomarkers of natalizumab treatment and PML risk.
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
The underlying etiology for the association of natalizumab therapy to an increase risk of progressive multifocal leukoencephalopathy (PML) remains unknown.
It is possible that persistently high natalizumab levels lead to sustained immune-modulation or suppression resulting in an increased PML risk.
Since 2010 we have conducted three investigator initiated trials (IITs) at our center to measure serum natalizumab concentration, lymphocyte alpha 4 integrin saturation, and other biomarkers to understand the association of these markers to PML risk.
A number of the patients who participated in these clinical trials are still infusing.
These studies have demonstrated that plasma natalizumab concentrations continue to rise over time with a plateau effect not yet clearly delineated.
Improved drug clearance in patients with higher body weight is described in the prescribing information.
We have accumulated preliminary data suggesting that patients with lower body weight may be at higher risk for PML and that this may relate to higher drug concentrations and saturations seen in this group.
Dose extension may be a viable option to lower drug concentration (pharmacokinetic, PK) and saturation (pharmacodynamic, PD) in patients with lower body weight to potentially impact PML incidence.
In addition to the PK/PD of natalizumab, host related biomarkers may allow for more specific PML risk stratification.
Further validation of these biomarkers is critical for our understanding of their utility.
Type d'étude
Observationnel
Inscription (Réel)
196
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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Utah
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Salt Lake City, Utah, États-Unis, 84103
- Rocky Mountain MS Research Group
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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
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
Up to 200 patients with relapsing forms of multiple sclerosis.
All subjects will receive open label natalizumab according to their prescribing physician.
La description
Inclusion Criteria:
- Ability to understand the purpose and risks of the study and provide signed and dated consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
- Must be enrolled in the TOUCH Prescribing Program for Tysabri® (natalizumab) prior to informed consent.
- In the opinion of the Principal Investigator, must be able and willing to comply with all study directions
- ≥ 18 years of age at the time of informed consent
Exclusion Criteria:
- In the opinion of the Principal Investigator, subject is unwilling or unable to comply with study directions.
Subject who is pregnant, breastfeeding, or likely to becoming pregnant during the course of the study. Women of child-bearing potential must be practicing an acceptable form of birth control.
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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
- Modèles d'observation: Cohorte
- Perspectives temporelles: Autre
Cohortes et interventions
Groupe / Cohorte |
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Group A: Natalizumab Naïve
This group will consist of up to 10 people who are naïve to natalizumab (haven't received the drug before) and are just beginning therapy.
These participants will meet with the study staff at Week 0 (Baseline) prior to their natalizumab infusion.
They will then have a follow up appointment every 3 months for the first 12 months of their natalizumab infusions, for a total of 5 visits.
Natalizumab concentration and other biomarkers will be measured at each visit.
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Group B: Intracycle Regular Dosing
This group will consist of at least 50 people who are on a regular infusing cycle of 28-31 days.
These participants will be consented at Week 0 (Baseline) and asked to come back each week during their regular cycle at Week 1, Week 2, and Week 3, for a total of 4 study visits.
Natalizumab concentration and other biomarkers will be measured during their participation in the study.
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Group C: Intracycle Extended Dosing
This group will consist of up to 60 people who are on an extended infusing cycle of greater than 30 days.
These participants will be consented at Week 0 (Baseline) and asked to come back each week for a blood draw to measure Natalizumab concentration and other biomarkers during their extended cycle at Week 2, and Week 4, for a total of 3 study visits.
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Group D: Transition Dosing
This group will consist of up to 10 people who are on a regular infusing cycle of 28-30 days who will be transitioning to an extended dosing cycle.
The decision to transition will be made by their treating neurologist.
These participants will be consented at Week 0 (Baseline) and will be followed for 8 cycles.
Natalizumab concentration will be measured at each cycle.
During certain cycles, other biomarkers will be measured.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Pharmacokinetic (PK) Changes over Time
Délai: 12 month
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Changes in natalizumab concentration (ug/ml) will be collected and compared to similar infusion cycle lengths collected previously in investigator-initiated trials at this site.
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12 month
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Pharmacodynamic (PD) Changes over Time
Délai: 12 month
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Changes in natalizumab saturation (%) will be collected and compared to similar infusion cycle lengths collected previously in investigator-initiated trials at this site.
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12 month
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: John F Foley, MD, Rocky Mountain MS Research Group, LLC
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
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
1 octobre 2014
Achèvement primaire (Réel)
1 mars 2017
Achèvement de l'étude (Réel)
1 juillet 2020
Dates d'inscription aux études
Première soumission
16 octobre 2014
Première soumission répondant aux critères de contrôle qualité
6 mai 2015
Première publication (Estimation)
12 mai 2015
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
21 février 2021
Dernière mise à jour soumise répondant aux critères de contrôle qualité
17 février 2021
Dernière vérification
1 février 2021
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- SRA-001
Plan pour les données individuelles des participants (IPD)
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Non
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